Antibiotic and anti-inflammatory use and the risk of prostate cancer

<p>Abstract</p> <p>Background</p> <p>Prostate inflammation or infection may increase the risk of prostate cancer. Antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat prostatitis and urinary tract infections (UTIs). The objective of our study was to assess whether their use decreases the risk of prostate cancer.</p> <p>Methods</p> <p>We conducted a case-control study among men with incident prostate cancer (N = 65 cases) and without prostate cancer (N = 195 controls) at the San Francisco Veteran Affairs medical center (VAMC) between June 1996 and June 2006. Cases were all patients who had prostate biopsies positive for cancer. We matched controls to cases on age group and race at a 3:1 ratio, and each matched pair was given an identical index date. Total antibiotic, aspirin, and NSAID use (number of prescriptions) was computed for each participant by drug type and was restricted to a fill date at least 1 year before the index date. Logistic regression was used for analysis. We adjusted for the matching variables (age group and race) and potential confounders (years of VAMC enrollment and number of clinic visits).</p> <p>Results</p> <p>Neither total antibiotic use nor total anti-inflammatory use reduces the risk of prostate cancer (<it>P </it>> 0.05).</p> <p>Conclusion</p> <p>Our analysis did not reveal a relation between use of antibiotics, aspirin, or NSAIDs and the risk of prostate cancer.</p

Developing an Intervention Toolbox for the Common Health Problems in the Workplace

Development of the Health ↔ Work Toolbox is described. The toolbox aims to reduce the workplace impact of common health problems (musculoskeletal, mental health, and stress complaints) by focusing on tackling work-relevant symptoms. Based on biopsychosocial principles this toolbox supplements current approaches by occupying the zone between primary prevention and healthcare. It provides a set of evidence-informed principles and processes (knowledge + tools) for tackling work-relevant common health problems. The toolbox comprises a proactive element aimed at empowering line managers to create good jobs, and a ‘just in time’ responsive element for supporting individuals struggling with a work-relevant health problem. The key intention is helping people with common health problems to maintain work participation. The extensive conceptual and practical development process, including a comprehensive evidence review, produced a functional prototype toolbox that is evidence based and flexible in its use. End-user feedback was mostly positive. Moving the prototype to a fully-fledged internet resource requires specialist design expertise. The Health ↔ Work Toolbox appears to have potential to contribute to the goal of augmenting existing primary prevention strategies and healthcare delivery by providing a more comprehensive workplace approach to constraining sickness absence

Comparison of X-Ray, Millimeter Wave, Shearography and Through-Transmission Ultrasonic Methods for Inspection of Honeycomb Composites

Honeycomb composites are increasingly finding utility in a variety of environments and applications, such as aircraft structural components, flight control components, radomes, etc. In-service and environmental stresses can produce unwanted flaws that adversely affect the structural integrity and functionality of these composites. These flaws may be in the forms of disbonds, delaminations, impact damage, crushed honeycomb, moisture intrusion, internal cracks, etc. There are several nondestructive testing (NDT) methods that may be used to inspect these composites for the presence and evaluation of these flaws. Such NDT methods include X-ray computed tomography, near-field millimeter wave, shearography, and ultrasonic testing. To assess the capabilities of these methods for honeycomb composite inspection, two honeycomb composites panels were produced with several embedded flaws and missing material primarily representing planar disbonds at various levels within the thickness of the panels and with different shapes. Subsequently, the aforementioned NDT methods were used to produce images of the two panels. This paper presents the results of these investigations and a comparison among the capabilities of these methods

Passing the acid test? Evaluating the impact of national education initiatives to reduce proton pump inhibitor use in Australia

Publisher's version (útgefin grein)Background Proton pump inhibitor (PPI) use is widespread. There have been increasing concerns about overuse of high-dose PPIs for durations longer than clinically necessary. Objective To evaluate the impact of national education initiatives on reducing PPI use in Australia. Design Population-based, controlled interrupted time series analysis of PPI dispensing claims data for Australian adults from July 2012 to June 2018; we used statin dispensing as a control. Interventions A year-long educational initiative led by NPS MedicineWise (previously the National Prescribing Service) from April 2015. Simultaneously, Choosing Wisely released recommendations in April 2015 and May 2016. Both promoted review of prolonged PPI use and encouraged stepping down or ceasing treatment, where appropriate. Measurements We examined monthly changes in PPI (and statin) dispensing (stratified by high, standard and low tablet strength), rates of switching from higher to lower strength PPIs and rates of PPI (and statin) discontinuation. Results We observed 12 040 021 PPI dispensings to 579 594 people. We observed a sustained -1.7% (95% CI: -2.7 to -0.7%) decline in monthly dispensing of standard strength PPIs following the initiatives until the end of the study period. There were no significant changes in high or low strength PPI (or statin) dispensings, switching to lower strength PPIs, or PPI (and statin) treatment discontinuation. Conclusion Our findings suggest that these educational initiatives alone were insufficient in curbing overuse of PPIs on a national level. Concerted efforts with policy levers such as imposing tighter restrictions on subsidised use of PPIs may be more effective. Noting low strength esomeprazole is not publicly subsidised in Australia, availability of these preparations may also facilitate more appropriate practiceThis research is supported by the National Health and Medical Research Council (NHMRC) Centre of Research Excellence in Medicines and Ageing (ID: 1060407) and a Cooperative Research Centre Project (CRC-P) Grant from the Australian Government Department of Industry, Innovation and Science (ID: CRC-P-439). Dr Zoega was supported by a Scientia Fellowship from UNSW Sydney. Dr Schaffer was supported by a NHMRC Early Career Fellowship (#1158763).Peer Reviewe

A comparison of quantitative methods for clinical imaging with hyperpolarized (13)C-pyruvate.

Dissolution dynamic nuclear polarization (DNP) enables the metabolism of hyperpolarized (13)C-labelled molecules, such as the conversion of [1-(13)C]pyruvate to [1-(13)C]lactate, to be dynamically and non-invasively imaged in tissue. Imaging of this exchange reaction in animal models has been shown to detect early treatment response and correlate with tumour grade. The first human DNP study has recently been completed, and, for widespread clinical translation, simple and reliable methods are necessary to accurately probe the reaction in patients. However, there is currently no consensus on the most appropriate method to quantify this exchange reaction. In this study, an in vitro system was used to compare several kinetic models, as well as simple model-free methods. Experiments were performed using a clinical hyperpolarizer, a human 3 T MR system, and spectroscopic imaging sequences. The quantitative methods were compared in vivo by using subcutaneous breast tumours in rats to examine the effect of pyruvate inflow. The two-way kinetic model was the most accurate method for characterizing the exchange reaction in vitro, and the incorporation of a Heaviside step inflow profile was best able to describe the in vivo data. The lactate time-to-peak and the lactate-to-pyruvate area under the curve ratio were simple model-free approaches that accurately represented the full reaction, with the time-to-peak method performing indistinguishably from the best kinetic model. Finally, extracting data from a single pixel was a robust and reliable surrogate of the whole region of interest. This work has identified appropriate quantitative methods for future work in the analysis of human hyperpolarized (13)C data.CJD is jointly funded by the National Institute for Health Research (NIHR), Cambridge Biomedical Research Centre and GlaxoSmithKline (GSK). Additional funding for this study was provided by Cancer Research UK (CRUK, C19212/A16628; C19212/A911376), The Wellcome Trust, Cambridge Experimental Cancer Medicine Centre, Cambridge Cancer Centre, the School of Clinical Medicine at the University of Cambridge and the CRUK and Engineering and Physical Sciences Research Council (EPSRC) Cancer Imaging Centre in Cambridge and Manchester.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/nbm.346

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies

Foodborne disease outbreaks in United States schools

Background. The objective of this study was to describe the epidemiology of foodborne disease outbreaks in schools and to identify where preventive measures could be targeted. Methods. Reports by state and local health departments of foodborne disease outbreaks occurring in primary and secondary schools, colleges and universities from January 1, 1973, through December 31, 1997, were reviewed. Data from ill persons identified through foodborne outbreak investigations and subsequently reported to the Centers for Disease Control and Prevention in the Foodborne Outbreak Surveillance System were examined. The number and size of foodborne disease outbreaks, as well as the etiologic agents, food vehicles of transmission, site of food preparation and contributing factors associated with outbreaks were also examined. Results. From 1973 through 1997, states and local health departments reported 604 outbreaks of foodborne disease in schools. The median number of school outbreaks annually was 25 (range, 9 to 44). In 60% of the outbreaks an etiology was not determined, and in 45% a specific food vehicle of transmission was not determined. Salmonella was the most commonly identified pathogen, accounting for 36% of outbreak reports with a known etiology. Specific food vehicles of transmission were epidemiologically identified in 333 (55%) of the 604 outbreaks. The most commonly implicated vehicles were foods containing poultry (18.6%), salads (6.0%), Mexican-style food (6.0%), beef (5.7%) and dairy products excluding ice cream (5.0%). The most commonly reported food preparation practices that contributed to these school-related outbreaks were improper food storage and holding temperatures and food contaminated by a food handler. Conclusions. Strengthening food safety measures in schools would better protect students and school staff from outbreaks of foodborne illness. Infection control policies, such as training and certification of food handlers in the proper storage and cooking of foods, meticulous hand washing and paid sick leave for food handlers with gastroenteritis, could make meals safer for American students

Identification and Functional Validation of the Novel Antimalarial Resistance Locus PF10_0355 in Plasmodium falciparum

The Plasmodium falciparum parasite's ability to adapt to environmental pressures, such as the human immune system and antimalarial drugs, makes malaria an enduring burden to public health. Understanding the genetic basis of these adaptations is critical to intervening successfully against malaria. To that end, we created a high-density genotyping array that assays over 17,000 single nucleotide polymorphisms (~1 SNP/kb), and applied it to 57 culture-adapted parasites from three continents. We characterized genome-wide genetic diversity within and between populations and identified numerous loci with signals of natural selection, suggesting their role in recent adaptation. In addition, we performed a genome-wide association study (GWAS), searching for loci correlated with resistance to thirteen antimalarials; we detected both known and novel resistance loci, including a new halofantrine resistance locus, PF10_0355. Through functional testing we demonstrated that PF10_0355 overexpression decreases sensitivity to halofantrine, mefloquine, and lumefantrine, but not to structurally unrelated antimalarials, and that increased gene copy number mediates resistance. Our GWAS and follow-on functional validation demonstrate the potential of genome-wide studies to elucidate functionally important loci in the malaria parasite genome.Bill & Melinda Gates FoundationEllison Medical FoundationExxon Mobil FoundationFogarty International CenterNational Institute of Allergy and Infectious Diseases (U.S.)Burroughs Wellcome FundDavid & Lucile Packard FoundationNational Science Foundation (U.S.). Graduate Research Fellowship Progra