Prostate Cancer Screening Practices and Knowledge of Prostate Cancer Screening Clinical Practice Guidelines By Primary Care Physicians: A Systematic Review of the Literature and Original Research Design

Objectives: The purpose of this paper is to systematically examine the literature regarding primary care physicians' knowledge and practice style concerning prostate cancer screening. I will then use the information to develop a research plan to assess physician practice styles, beliefs, and knowledge of recent guidelines and scientific evidence regarding prostate cancer screening. Methods: I conducted a systematic evidence review to determine whether American primary care physicians are using shared decision-making when doing prostate cancer screening and which clinical practice guidelines (CPGs) they are aware of. I used a Medline search. Cross-sectional studies were included in the review. Randomized controlled trials, cohort studies and case-control studies would have been accepted except none were found. The main outcomes of interest were physicians' prostate cancer screening style specifically if they do pretest counseling (including shared decision-making), and knowledge of prostate cancer screening guidelines. Shared decision-making was defined as physicians doing prescreening discussions of the risks and benefits of prostate cancer screening and allowing their patients to participate in the decision whether or not to proceed with screening to the level the patient desired. Results: Seven studies were included in the final review, none were done since the most recent guideline updates issued in 2008 and 2009 and none looked at knowledge of recent evidence from two large randomized controlled trials (RCT) on mortality benefit of PSA screening that were published in March of 2009. Several themes emerged from the literature review of studies published since 2000. It showed that between 60% and I 00% of physicians report using shared decision-making. The 100% was from a focus group study, whereas in surveys between 66% and 99% of physicians report using shared decision-making. Physicians with knowledge of the guidelines or the unclear evidence of benefit are more likely to use shared decision-making than those without the knowledge. And between 0% and 33% of men age 50 and over are being screened for prostate cancer without a prescreening discussion of risks and benefits. No studies compared knowledge of guidelines to practice style. Conclusion: Primary care physicians with greater knowledge of the insufficient evidence for prostate cancer screening are more likely than those lacking knowledge to be practicing shared decision-making. Since all of the studies were done prior to 2009, it is not clear whether physicians have knowledge of the newest CPGs and randomized-control trial evidence for prostate cancer screening. Yet, the results of this review show that knowledge of the latest developments is likely to influence practice. Our research study is designed to assess the knowledge of the newest evidence and guidelines and the effect this has had on physician belief of benefit of prostate cancer screening. The primary outcomes will be knowledge of the mortality studies and current guideline, reported influence of the 2009 RCTs of prostate cancer screening on practice style, any association between knowledge of the RCTs or guidelines and belief of benefit of prostate cancer screening, and any association between knowledge of the mortality studies on practice style. We will also assess the way physicians report learning about the RCTs and any association between reported knowledge and correct knowledge answers with method of learning about the RCTs.Master of Public Healt

Structure-based Predictions for Molecular Initiating Events

Toxicity testing of chemicals is currently undergoing its largest ever paradigm shift, moving towards faster, cheaper and more human-relevant methods which focus on mechanistic understanding. An AOP provides a framework for organising biological knowledge and data. The gateway to an AOP is the MIE, and chemistry is key to predicting which chemicals can undergo a MIE. In silico predictions of MIEs are a vital tool in a modern, mechanism-focused approach to risk assessment of chemicals. In this project, new structural alert-based models for receptor binding MIEs have been constructed that create accurate, transparent and interpretable predictions. The alerts have been constructed with an automated workflow that uses Bayesian statistics to iteratively select substructures associated with activity. The models were constructed from balanced data sets taken from human in vitro¬ assays in the ChEMBL and ToxCast databases. The new models significantly improve on previous models, with performance metrics comparable to random forest models. Methods for further improving structural alert models are presented, including a method for generalising aromatic atoms in structural alerts to reduce the number of alerts in a model, and construction of a consensus model combining structural alerts with a random forest model. Structural alert models have been constructed for a wide range of biological targets of toxicological interest and the variation in performance across all targets has been explained by considering the proportion of activity cliffs in data sets. Having significantly improved structural alert models in terms of performance, new methods for assessing confidence in both active and inactive predictions have been developed. These involve considering similarity to relevant chemicals in the training set. The measure of confidence in active predictions allows for applicability of predictions to be evaluated, whilst the measure of confidence in inactive predictions is vital in risk assessment of chemicals. Moving beyond structural alerts, attempts to describe chemicals in terms of the key interactions made with the biological target have been made. This a step towards describing how the receptor binding MIEs work and then using this knowledge to make better activity predictions. The generalised aromatic structural alerts have been used to predict key receptor binding interactions, which are consistent with interactions derived from crystal structures. Using structural alerts to group chemicals, pharmacophore models have been developed, allowing for activity predictions in terms of general features in three-dimensional space instead of the specific combination of atoms and bonds described by structural alerts.Unileve

The detection of patients at risk of gastrointestinal toxicity during pelvic radiotherapy by electronic nose and FAIMS : a pilot study

It is well known that the electronic nose can be used to identify differences between human health and disease for a range of disorders. We present a pilot study to investigate if the electronic nose and a newer technology, FAIMS (Field Asymmetric Ion Mobility Spectrometry), can be used to identify and help inform the treatment pathway for patients receiving pelvic radiotherapy, which frequently causes gastrointestinal side-effects, severe in some. From a larger group, 23 radiotherapy patients were selected where half had the highest levels of toxicity and the others the lowest. Stool samples were obtained before and four weeks after radiotherapy and the volatiles and gases emitted analysed by both methods; these chemicals are products of fermentation caused by gut microflora. Principal component analysis of the electronic nose data and wavelet transform followed by Fisher discriminant analysis of FAIMS data indicated that it was possible to separate patients after treatment by their toxicity levels. More interestingly, differences were also identified in their pre-treatment samples. We believe these patterns arise from differences in gut microflora where some combinations of bacteria result to give this olfactory signature. In the future our approach may result in a technique that will help identify patients at “high risk” even before radiation treatment is started

La estrangulación carotídea: dormir, ¿tal vez morir?

Este es un examen de la estrangulación carotidea, también conocida como la “presa durmiente”. Nos preocuparemos de los tipos de agarres durmientes y de qué parte del cuello se ve afectada y cómo. Se denomina habitualmente “estrangulación sanguínea”. Existe una diferenciación entre las estrangulaciones sanguíneas y las estrangulaciones respiratorias. Este artículo tratará la aplicación, efectos, resultados a corto y largo plazo, y ramificaciones respecto a la utilización de drogas y al estado mental. No incluiremos los efectos de una estrangulación sobre la tráquea, o de la presión o los golpes a la parte posterior del cuello. Este artículo se presenta desde dos perspectivas; la del practicante/ instructor de artes marciales y la del médico

Characteristics of temporal patterns of cortisol and luteinizing hormone in primiparous, postpartum, anovular, suckled, beef cows exposed acutely to bulls

BACKGROUND: The physiological mechanism by which bulls stimulate resumption of ovarian cycling activity in postpartum, anovular, suckled cows after calving may involve the concurrent activation of the hypothalamic-hypophyseal-ovarian (HPO) axis and hypothalamic-hypophyseal-adrenal (HPA) axis. Thus, the objectives of this experiment were to determine if characteristics of temporal patterns of cortisol and luteinizing hormone (LH) in postpartum, anovular, beef cows are influenced by acute exposure to bulls. The null hypotheses were that daily, temporal characteristics of cortisol and LH concentration patterns do not differ between cows exposed acutely to bulls or steers. METHODS: Sixteen cows were assigned randomly 67 +/- 4 (+/- SE) after calving to be exposed to bulls (EB, n = 8) or steers (ES, n = 8) 5 h daily for 9 d (D 0 to 8). Blood samples were collected daily from each cow via jugular catheters at 15-min intervals for 6 h from 1000 to 1600 h each day. The 5-h exposure period began 1 h after the start of the intensive bleeding period. Characteristics of cortisol and LH concentration patterns (mean, baseline, pulse frequency, pulse amplitude, and pulse duration) were identified by PULSAR analyses. RESULTS: Mean cortisol concentrations decreased (P < 0.05) in cows in both treatments from D 0 to D 2. Thereafter, mean cortisol concentrations stabilized and did not differ (P > 0.10) between EB and ES cows. The decrease in mean cortisol concentrations in EB and ES cows from D 0 to D 2 was attributed to cows acclimatizing to intensive blood sampling and handling procedures. Consequently, analyses for characteristics of cortisol and LH concentration patterns included D 2 through 8 only. Cortisol mean and baseline concentrations, and pulse amplitude did not differ (P > 0.10) between EB and ES cows. However, cortisol pulse duration tended to be longer (P = 0.09) and pulse frequency was lower (P = 0.05) in EB than ES cows. LH pulse frequency was greater (P = 0.06) in EB than ES cows. All other characteristics of LH concentration patterns did not differ (P > 0.10) between EB and ES cows. Characteristics of cortisol concentration patterns were not related to characteristics of LH concentration patterns for ES cows (P > 0.10). However, as cortisol pulse amplitude increased, LH pulse amplitude decreased (b1 = -0.04; P < 0.05) for EB cows. CONCLUSIONS: In conclusion, exposing primiparous, postpartum, anovular, suckled cows to bulls for 5-h daily over a 9-d period did not alter mean concentrations of cortisol or LH compared to mean concentrations of cortisol and LH in cows exposed to steers. However, exposing cows to bull in this manner altered characteristics of temporal patterns of both LH and cortisol by increasing LH pulse frequency and decreasing cortisol pulse frequency. Interestingly, in cows exposed to bulls, as amplitude and frequency of cortisol pulses decreased, amplitudes of LH pulses increased and frequency of LH pulses tended to increase. Thus, the physiological mechanism of the biostimulatory effect of bulls may initially involve modification of the HPA axis and these changes may facilitate activation of the HPO axis and resumption of ovulatory cycles in postpartum, anovular, suckled cows

What do readers want?:Results of an online survey to involve readers in updating the seventh edition of the Manual of dietetic practice

BACKGROUND: The Manual of dietetic practice ('Manual') is the core textbook for qualified and student dietitians. A survey was conducted to explore views on the scope, content and presentation of the Manual to inform the forthcoming edition. METHODS: The survey comprised of questions on demographics, structure, content, access (print/digital), missing topics, strengths and weaknesses. It was distributed to members of the British Dietetic Association (BDA) and other relevant groups in August 2022. Responses are presented as frequencies and free text as themes. RESULTS: Of 1179 responses, 91% were from professionals, of whom 72% were registered dietitians with a mean of 12.7 years (range: 1-44) in practice: 60% worked in the United Kingdom with 52% based in a clinical setting. The printed version was preferred: 59% professionals, 60% students, 94% professionals and 88% students were satisfied with the structure; however, 26% professionals and 22% students identified content that was lacking or outdated, including mental health and sustainability. The strengths were its comprehensive coverage and respected contributing authors. Weaknesses included the cost, size, lack of visual aids and currency. Professionals indicated the seventh edition should focus on more practical information required for clinical practice, whereas students wanted more emphasis on summarised information and visual formats. CONCLUSIONS: The survey proved a valuable method to engage with the readership to ensure the next edition reflected their requirements. Although nearly all respondents were satisfied with the scope and content, the results highlighted those topics lacking and/or outdated. Results also showed that the next edition should focus on practical information required for clinical practice, with more summarised and visual formats

Development of machine learning support for reading whole body diffusion-weighted MRI (WB-MRI) in myeloma for the detection and quantification of the extent of disease before and after treatment (MALIMAR): protocol for a cross-sectional diagnostic test accuracy study.

INTRODUCTION: Whole-body MRI (WB-MRI) is recommended by the National Institute of Clinical Excellence as the first-line imaging tool for diagnosis of multiple myeloma. Reporting WB-MRI scans requires expertise to interpret and can be challenging for radiologists who need to meet rapid turn-around requirements. Automated computational tools based on machine learning (ML) could assist the radiologist in terms of sensitivity and reading speed and would facilitate improved accuracy, productivity and cost-effectiveness. The MALIMAR study aims to develop and validate a ML algorithm to increase the diagnostic accuracy and reading speed of radiological interpretation of WB-MRI compared with standard methods. METHODS AND ANALYSIS: This phase II/III imaging trial will perform retrospective analysis of previously obtained clinical radiology MRI scans and scans from healthy volunteers obtained prospectively to implement training and validation of an ML algorithm. The study will comprise three project phases using approximately 633 scans to (1) train the ML algorithm to identify active disease, (2) clinically validate the ML algorithm and (3) determine change in disease status following treatment via a quantification of burden of disease in patients with myeloma. Phase 1 will primarily train the ML algorithm to detect active myeloma against an expert assessment ('reference standard'). Phase 2 will use the ML output in the setting of radiology reader study to assess the difference in sensitivity when using ML-assisted reading or human-alone reading. Phase 3 will assess the agreement between experienced readers (with and without ML) and the reference standard in scoring both overall burden of disease before and after treatment, and response. ETHICS AND DISSEMINATION: MALIMAR has ethical approval from South Central-Oxford C Research Ethics Committee (REC Reference: 17/SC/0630). IRAS Project ID: 233501. CPMS Portfolio adoption (CPMS ID: 36766). Participants gave informed consent to participate in the study before taking part. MALIMAR is funded by National Institute for Healthcare Research Efficacy and Mechanism Evaluation funding (NIHR EME Project ID: 16/68/34). Findings will be made available through peer-reviewed publications and conference dissemination. TRIAL REGISTRATION NUMBER: NCT03574454

Analysis of 61 exclusive enteral nutrition formulas used in management of active Crohn's disease - new insights into dietary disease triggers

Background: Exclusive enteral nutrition (EEN) is an effective treatment for Crohn's disease. Aims: To investigate the hypothesis that ingredients of EEN formulas are unlikely to initiate a disease flare and that their dietary elimination is not essential for disease amelioration. Methods: We performed compositional analysis of EEN formulas with evidence of efficacy in management of active Crohn's disease. Macronutrient content was compared against the dietary reference values (DRV), the UK National Diet and Nutrition Survey (NDNS) and intake of Crohn's disease children. Food additives were cross‐referenced against the FAO/WHO database. Results: Sixty‐one formulas were identified with variable composition (carbohydrates [22.8%‐89.3%], protein [7.8%‐30.1%], fat [0%‐52.5%]). Maltodextrin, milk protein and vegetable/plant oils were the commonest macronutrient sources. Their n‐6:n‐3 fatty acid ratio varied from 0.25 to 46.5. 56 food additives were identified (median per formula: 11). All formulas were lactose‐free, gluten‐free, and 82% lacked fibre. The commonest food additives were emulsifiers, stabilisers, antioxidants, acidity regulators and thickeners. Food additives, implicated in Crohn's disease aetiology, were present in formulas (modified starches [100%], carrageenan [22%], carboxymethyl cellulose [13%] and polysorbate 80 [5%]). Remission rates did not differ between EEN formulas with and without those food additives. Analysis including only formulas from randomised controlled trials (RCTs) retained in the latest Cochrane meta‐analysis produced similar findings. EEN formulas contained less energy from saturated fat than NDNS intake. Conclusion: We have identified food ingredients which are present in EEN formulas that are effective in Crohn's disease and challenge perceptions that these ingredients might be harmful

Online Quantification of Criegee Intermediates of α-Pinene Ozonolysis by Stabilization with Spin Traps and Proton-Transfer Reaction Mass Spectrometry Detection

Biogenic alkenes, which are among the most abundant volatile organic compounds in the atmosphere, are readily oxidized by ozone. Characterizing the reactivity and kinetics of the first-generation products of these reactions, carbonyl oxides (often named Criegee intermediates), is essential in defining the oxidation pathways of organic compounds in the atmosphere but is highly challenging due to the short lifetime of these zwitterions. Here, we report the development of a novel online method to quantify atmospherically relevant Criegee intermediates (CIs) in the gas phase by stabilization with spin traps and analysis with proton-transfer reaction mass spectrometry. Ozonolysis of α-pinene has been chosen as a proof-of-principle model system. To determine unambiguously the structure of the spin trap adducts with α-pinene CIs, the reaction was tested in solution, and reaction products were characterized with high-resolution mass spectrometry, electron paramagnetic resonance, and nuclear magnetic resonance spectroscopy. DFT calculations show that addition of the Criegee intermediate to the DMPO spin trap, leading to the formation of a six-membered ring adduct, occurs through a very favorable pathway and that the product is significantly more stable than the reactants, supporting the experimental characterization. A flow tube set up has been used to generate spin trap adducts with α-pinene CIs in the gas phase. We demonstrate that spin trap adducts with α-pinene CIs also form in the gas phase and that they are stable enough to be detected with online mass spectrometry. This new technique offers for the first time a method to characterize highly reactive and atmospherically relevant radical intermediates in situ.This work was funded by the European Research Council (ERC starting grant 279405). Authors thank four anonymous reviewers for helpful revision of the manuscript

Validation of the Rome III criteria for the diagnosis of irritable bowel syndrome in secondary care

BACKGROUND & AIMS: There are few validation studies of existing diagnostic criteria for irritable bowel syndrome (IBS). We conducted a validation study of the Rome and Manning criteria in secondary care. METHODS: We collected complete symptom, colonoscopy, and histology data from 1848 consecutive adult patients with gastrointestinal symptoms at 2 hospitals in Hamilton, Ontario; the subjects then underwent colonoscopy. Assessors were blinded to symptom status. Individuals with normal colonoscopy and histopathology results, and no evidence of celiac disease, were classified as having no organic gastrointestinal disease. The reference standard used to define the presence of true IBS was lower abdominal pain or discomfort in association with a change in bowel habit and no organic gastrointestinal disease. Sensitivity, specificity, and positive and negative likelihood ratios, with 95% confidence intervals, were calculated for each diagnostic criteria. RESULTS: In identifying patients with IBS, sensitivities of the criteria ranged from 61.9% (Manning) to 95.8% (Rome I), and specificities from 70.6% (Rome I) to 81.8% (Manning). Positive likelihood ratios ranged from 3.19 (Rome II) to 3.39 (Manning), and negative likelihood ratios from 0.06 (Rome I) to 0.47 (Manning). The level of agreement between diagnostic criteria was greatest for Rome I and Rome II (κ = 0.95), and lowest for Manning and Rome III (κ = 0.59). CONCLUSIONS: Existing diagnostic criteria perform modestly in distinguishing IBS from organic disease. There appears to be little difference in terms of accuracy. More accurate ways of diagnosing IBS, avoiding the need for investigation, are required