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Sublethal heating can increase subsequent thermal resistance of bacteria, which may compromise the validity of thermal process validations for slow-roasted meats. Therefore, this research evaluated the accuracy of a traditional log-linear inactivation model, developed via prior laboratory-scale isothermal tests, and a novel path-dependent model accounting for sublethal injury, applied to pilot-scale slow cooking of whole-muscle roasts. Irradiated turkey breasts, beef rounds, and pork loins were inoculated with an eight-serovar Salmonella cocktail via vacuum tumble marination in a salt-phosphate marinade. The resulting initial Salmonella population in the geometric center (core) was 7.0, 6.3, and 6.3 log CFU/g for turkey, beef, and pork, respectively. Seven different cooking schedules representing industry practices were evaluated in a pilot-scale, moist-air convection oven. Core temperatures recorded during cooking were used to calculate lethality real-time via the log-linear model. The path-dependent model reduced the bias (mean residual) and root mean square error by 4.24 and 4.60 log CFU/g respectively, in turkey; however, the new model did not reduce the prediction error in beef or pork. Overall, results demonstrated that slow-cooked roasts, processed to a computed lethality at or near that required by the regulatory performance standards, as calculated with a state-dependent model, may be underprocessed. [ABSTRACT FROM AUTHOR]

This paper presents a comparative analysis of Outpatient Parenteral Antimicrobial Therapy (OPAT) structures and delivery options across different countries. OPAT, a cost-effective alternative to inpatient care for patients requiring IV antimicrobial therapy, has demonstrated multiple benefits such as patient satisfaction, economic cost savings, and reduced hospital-acquired infections. Despite these advantages, there is considerable international variation in OPAT use and implementation. By examining the OPAT structures of multiple countries, we aim to identify areas of variation and explore opportunities for expansion and improvement of OPAT services., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Competing Interests: None declared

The production of anthropomorphic phantoms generated from tissue-equivalent materials is challenging but offers an excellent copy of the typical environment encountered in typical patients. High-quality dosimetry measurements and the correlation of the measured dose with the biological effects elicited by it are a prerequisite in preparation of clinical trials with novel radiotherapy approaches. We designed and produced a partial upper arm phantom from tissue-equivalent materials for use in experimental high-dose-rate radiotherapy. The phantom was compared to original patient data using density values and Hounsfield units obtained from CT scans. Dose simulations were conducted for broad-beam irradiation and microbeam radiotherapy (MRT) and compared to values measured in a synchrotron radiation experiment. Finally, we validated the phantom in a pilot experiment with human primary melanoma cells.

Objective:  To evaluate the evidence and produce a summary and recommendations for the most common heart and lung point-of-care ultrasound (PoCUS)., Methods:  We reviewed 10 clinical domains/questions related to common heart and lung applications of PoCUS. Following review of the evidence, a summary and recommendations were produced, including assigning levels of evidence (LoE) and grading of recommendation, assessment, development, and evaluation (GRADE). 38 international experts, the expert review group (ERG), were invited to review the evidence presented for each question. A level of agreement of over 75 % was required to progress to the next section. The ERG then reviewed and indicated their level of agreement of the summary and recommendation for each question (using a 5-point Likert scale), which was approved in the case of a level of agreement of greater than 75 %. A level of agreement was defined as a summary of "strongly agree" and "agree" on the Likert scale responses., Findings and Recommendations:  One question achieved a strong consensus for an assigned LoE of 3 and a weak GRADE recommendation (question 1), the remaining 9 questions achieved broad agreement with an assigned LoE of 4 and a weak GRADE recommendation (question 2), three achieved an LoE of 3 with a weak GRADE recommendation (questions 3-5), three achieved an LoE of 3 with a strong GRADE recommendation (questions 6-8) and the remaining two were assigned an LoE of 2 with a strong GRADE recommendation (questions 9 and 10)., Conclusion:  These consensus-derived recommendations should aid clinical practice and highlight areas of further research for PoCUS in acute settings., Competing Interests: A number of authors have declared potential conflicts of interest from the past three years.Bøetker, M.T. [royalties received from e-learning platform USabcd.org];Connolly, J. [honoraria received from Sonosite FujiFilm UK, equipment loans from Canon Healthcare, Terason Ultrasound, EchoNous]; Gargani, L. [honoraria received from GE Healthcare, Philips Healthcare & Caption Health]; Jarman, R.D. [honoraria received from Sonosite FujiFilm UK, equipment loans from Canon Healthcare];Kim, D. [medical advisor for Clarius Mobile Health]; Liu, R. [honoraria received from Philips Healthcare];Olusanya, O. [honoraria received from GE Healthcare & Sonosite FujiFilm UK];Peck, M. [honoraria received from GE Healthcare]., (Thieme. All rights reserved.)

Aims:  To evaluate the evidence and produce a summary and recommendations for the most common heart and lung applications of point-of-care ultrasound (PoCUS)., Methods:  We reviewed 10 clinical domains/questions related to common heart and lung applications of PoCUS. Following review of the evidence, a summary and recommendation were produced, including assignment of levels of evidence (LoE) and grading of the recommendation, assessment, development, and evaluation (GRADE). 38 international experts, the expert review group (ERG), were invited to review the evidence presented for each question. A level of agreement of over 75 % was required to progress to the next section. The ERG then reviewed and indicated their level of agreement regarding the summary and recommendation for each question (using a 5-point Likert scale), which was approved if a level of agreement of greater than 75 % was reached. A level of agreement was defined as a summary of "strongly agree" and "agree" on the Likert scale responses., Findings and Recommendations:  One question achieved a strong consensus for an assigned LoE of 3 and a weak GRADE recommendation (question 1). The remaining 9 questions achieved broad agreement with one assigned an LoE of 4 and weak GRADE recommendation (question 2), three achieving an LoE of 3 with a weak GRADE recommendation (questions 3-5), three achieved an LoE of 3 with a strong GRADE recommendation (questions 6-8), and the remaining two were assigned an LoE of 2 with a strong GRADE recommendation (questions 9 and 10)., Conclusion:  These consensus-derived recommendations should aid clinical practice and highlight areas of further research for PoCUS in acute settings., Competing Interests: A number of authors have declared potential conflicts of interest from the past three years:Bøetker, M.T. [royalties received from e-learning platform USabcd.org]; Connolly, J. [honoraria received from Sonosite FujiFilm UK, equipment loans from Canon Healthcare, Terason Ultrasound, EchoNous]; Gargani, L. [honoraria received from GE Healthcare, Philips Healthcare & Caption Health]; Jarman, R.D. [honoraria received from Sonosite FujiFilm UK, equipment loans from Canon Healthcare]; Kim, D. [medical advisor for Clarius Mobile Health]; Liu, R. [honoraria received from Philips Healthcare]; Olusanya, O. [honoraria received from GE Healthcare & Sonosite FujiFilm UK]; Peck, M. [honoraria received from GE Healthcare]., (Thieme. All rights reserved.)

Background and Purpose: Pneumothorax is a common presentation to acute healthcare services in Ireland, however there is wide variation in management approaches between centres. There is robust evidence to demonstrate that ambulatory management of pneumothorax is feasible and safe. The purpose of this study was to evaluate whether the implementation of an integrated care pathway (ICP) for pneumothorax patients with a focus on ambulatory care would be economically beneficial for the healthcare system., Methods: This study developed, implemented and evaluated an ICP for all patients presenting with pneumothorax, with a specific focus on ambulatory management for suitable patients. The ICP was designed to be utilised in the Irish healthcare setting, and was evaluated using a prospective multi-centre observational study, with a rigorous economic analysis at the centre of study design., Main Findings: Implementation of the ICP resulted in a statistically significant reduction in inpatient length of stay of 2.84 days from 7.4 to 4.56 days (p = 0.001). The incremental per patient cost reduction of treating a patient according to the pneumothorax ICP was 2314 euro. There were no adverse events related to drain insertion at the study sites., Conclusions: This study demonstrates therefore that standardisation of care for pneumothorax patients with a focus on ambulatory management are economically beneficial for the publicly-funded healthcare service. It is envisaged that this work will be used to inform healthcare policy at a national level across Ireland., Competing Interests: Declaration of competing interest None., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Despite the fact that health information is now more accessible than ever, knowledge gaps remain between patients and healthcare providers (HCPs). To date, the patients' need for information following a diagnosis of oesophageal cancer has not been adequately met., Purpose: The purpose of this study was to identify why knowledge gaps exist between oesophageal cancer patients and HCPs and how to address them., Methods: Purposive sampling of a group of people living with and after oesophageal cancer who had participated in a priority-setting partnership where 45% of questions from patients had existing evidence-based answers. A 7-set question series was developed for use in a patient/HCP focus group in addition to 11 individual phone interviews with survivors of oesophageal cancer. Qualitative semistructured interviews were conducted to explore oesophageal cancer patients' access to information. The data was analysed thematically, which involved coding all patient transcripts before identifying and reviewing key themes., Results: The three primary themes that emerged were as follows: opportunity (HCP team factors and relationship development), ability (patient factors) and priority (pacing of information delivery)., Conclusion: Effective communication between patients and HCPs was identified as an integral component of the enhancement of patient knowledge. HCPs should continue to refine and improve methods of information delivery and encourage conversations regarding information preferences., (© 2022. The Author(s).)

Rib fractures represent a substantial health burden. Chest injuries contribute to 25% of deaths after trauma and survivors can experience long-standing consequences, such as reduced functional capabilities and loss of employment. Over recent years, there has been an increase in the awareness of the importance of early identification, aggressive pain management and adequate safety netting for patients with chest injuries. Substandard management leads to increased rates of morbidity and mortality. The development of protocols in the emergency department (ED) for management of patients with chest wall injuries has demonstrated reduction of complication rates.Our aim was to develop an evidence-based, multidisciplinary chest injury pathway for the management of patients presenting with rib injury to our ED.Prior to implementation of the pathway in our department, only 39% of patients were documented as having received analgesia and only 7% of discharged patients had documented written verbal advice. There was no standardised method to perform regional anaesthetic blocks. Using quality improvement methods, we standardised imaging modality, risk stratification with a scoring system, analgesia with emphasis on regional anaesthesia blocks and disposition with information leaflets for those discharged.Implementation of the pathway increased rates of documented analgesia received from 39% to 70%. The number of regional anaesthetic blocks performed went from 0% to 60% and the number of patients receiving discharge advice went from 7% to 70%. Compliance of doctors and nurses with the pathway was 63%.Our previous audits showed substandard management of patients with chest injuries in our department. Through this quality improvement project, we were able to improve the quality of care provided to patients attending with rib fractures by increasing rate of analgesia received, regional blocks performed and discharge advice given., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim The fundamental concept of multidisciplinary education is a shared mental model that leads to better interdependent collaboration. The aim of this bootcamp was to create a sustainable induction curriculum for Anaesthesiology and Emergency Medicine trainees and nurses through training in a simulated multidisciplinary environment. Methods The two-day bootcamp consisted of lectures, equipment demonstration, workshops, and high-fidelity simulated scenarios. A pre- and post-course MCQ test was used for assessment of knowledge acquisition. Pre and post confidence scores were used to evaluate procedural skill confidence level. A 5-point Likert scale was used to evaluate qualitative feedback from participants. Results Seven anaesthesiology trainees, two anaesthetic nurses, six emergency medicine trainees and three emergency medicine nurses were enrolled. There was a statistically significant increase (p-value<0.01) in post-MCQ scores, portraying significant knowledge acquisition. The total procedural confidence scores increased from 375 (±9.15) to 550 (±8.43), (p < 0.01). All participants agreed that the stated educational objectives were met and relevant to their clinical practice, and strongly commended team training exercises. Conclusion Multidisciplinary simulation-based training improves team performance as well as transfer of knowledge across two or more disciplines. Overlapped training between Anaesthesiology and Emergency Medicine created an opportunity for sharing of educational resources in the current time-based speciality training system., Competing Interests: The authors declare that they have no competing interests.

Competing Interests: Conflict of interest The authors declare that there is no conflict of interests.

Background: Ambulatory management of isolated acute deep venous thrombosis (DVT) is the recommended standard of care in selected populations. However, in practice a significant number of patients continue to be managed as in-patients., Objectives: In this study we aimed to evaluate acute DVT treatment pathways in our emergency department (ED) in practice and to identify barriers to outpatient management., Methods: This study was a cross-sectional analysis of prospectively collected data pertaining to consecutive patients presenting to the ED of a large, city center, academic teaching hospital over a 46 week period who were diagnosed with DVT., Results: Implementation of an outpatient care pathway led to the majority of patients presenting with DVT in our institution being treated without hospital admission. Forty percent (31/78) of patients with DVT were treated with a direct oral anticoagulant (DOAC) as an outpatient in line with international best practice guidelines., Conclusion: The study provides a clear picture of the clinical profile and management of patients in clinical practice. Due to the lack of resources and supported infrastructure it is difficult to effectively implement outpatient venous thromboembolism (VTE) management to its full potential. Directing resources towards strategies which facilitate outpatient DVT treatment among vulnerable patient groups could represent a means of reducing hospital admissions for DVT in urban centers. Our study highlights the success and clinical limitations of the outpatient treatment model, which should become standard as part of wider VTE care., Competing Interests: Competing interestsThis study was partially supported by an unrestricted grant from Bayer pharmaceuticals.

Objectives: To determine the incidence of venous thromboembolism (VTE) and the incidence of hospital-acquired VTE (HA-VTE) arising within the population served by the Ireland East Hospital Group (IEHG)., Design: /home/user/Documents/Sathish Kumar G/RFO/June/21-06-2019/bmjopen_iss_9_7_20190621_1/ A retrospective observational study was conducted using hospital discharge data obtained from the hospital inpatient enquiry data reporting system. In this system, VTE events recorded as 'primary diagnosis' represented the reason for initial hospital admission, whereas VTE recorded as a 'secondary diagnosis' occurred following admission and were therefore used as an approximation of HA-VTE. These data were used to estimate the overall incidence of VTE and the proportion of these events which were hospital-acquired., Setting: The IEHG is the largest hospital group in the Irish healthcare system and serves a population of over 1 million individuals., Participants: Data were generated from records pertaining to the 2727 patient admission episodes where a diagnosis of VTE was made during the 22-month study period., Results: During the study period, 2727 VTE events were recorded within the IEHG (which serves a population of 1 036 279) corresponding to an incidence of 1.44 (95% CI 1.36 to 1.51) per 1000 per annum. 1273 (47%) of VTE events were recorded as secondary VTE. The incidence of VTE was highest among individuals over 85 years of age (16.03 per 1000;95% CI 12.81 to 19.26) and was more common following emergency hospital admission., Conclusion: These data suggest that HA-VTE accounts for at least 47% of all VTE events arising within a hospital group serving a population of over 1 million individuals within the Ireland. Given that HA-VTE is a well-recognised source of (potentially preventable) hospital deaths, these findings provide a compelling argument for prioritising strategies directed at reducing the risk of VTE among hospital patients served by the IEHG and within the Ireland as a whole., Competing Interests: Competing interests: FNA has received research funding from Leo Pharma and Bayer however these awards are not relevant to the current study., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In this prospective review of cancer screening in unselected patients with unprovoked venous thromboembolism (VTE) presenting to a large teaching hospital in the Republic of Ireland, we aimed to determine the effects of the implementation of the National Institute for Health and Care Excellence screening policy in a "real-world" population. Within our institution, 64 individuals presented with unprovoked VTE during the study period, of whom 47 underwent a screening computed tomography (CT) scan. Two cases of previously undiagnosed cancer were identified. However, in both cases, the clinical history provided by the affected individuals would have prompted a CT scan regardless of the recommendations of the screening policy. The screening CT scans identified 18 incidental lesions within the cohort, which required further diagnostic studies. None of the additional investigations completed to date have detected any lesion of clinical significance. These findings support the view that cancer screening with CT imaging in unselected individuals with unprovoked VTE is not justified or cost-effective.

Microbeam irradiation is spatially fractionated radiation on a micrometer scale. Microbeam irradiation with therapeutic intent has become known as microbeam radiation therapy (MRT). The basic concept of MRT was developed in the 1980s, but it has not yet been tested in any human clinical trial, even though there is now a large number of animal studies demonstrating its marked therapeutic potential with an exceptional normal tissue sparing effect. Furthermore, MRT is conceptually similar to macroscopic grid based radiation therapy which has been used in clinical practice for decades. In this review, the potential clinical applications of MRT are analysed for both malignant and non-malignant diseases.

Purpose: To evaluate locoregional recurrence (LRR) after mastectomy and impact of postmastectomy radiation (PMRT) by breast cancer subtype., Methods and Materials: Between 2000 and 2009, 5673 patients with stage I to III breast carcinoma underwent mastectomy and nodal evaluation; 30% received PMRT. Isolated LRR (iLRR) and LRR were compared across groups defined by biological subtype and receipt of trastuzumab: luminal A (estrogen [ER]/progesterone [PR]+, HER2-, low/intermediate grade), luminal B (ER/PR+, HER2-, high grade), HER2 with trastuzumab, HER2 without trastuzumab, and triple negative (TN; ER-, PR-, HER2-). LRR hazard ratios (HR) were estimated with multivariable Fine and Gray models. The effect of PMRT on LRR was evaluated with Fine and Gray models stratified by propensity for PMRT., Results: With a median follow-up time of 50.1 months, there were 19 iLRR and 109 LRR events. HER2 patients with trastuzumab had no iLRR and only a single LRR. Compared with luminal A patients, TN patients had significantly greater adjusted risk of iLRR (HR 14.10; 95% CI 2.97%-66.90%), with a similar trend among luminal B (HR 4.94; 95% CI 0.94%-25.82%) and HER2 patients without trastuzumab (HR 4.41; 95% CI 0.61%-32.11%). Although PMRT reduced LRR, the effect of PMRT varied by subgroup, with the greatest and smallest effects seen among luminal A (HR 0.17; 95% CI 0.05%-0.62%) and TN patients (HR 0.59; 95% CI 0.25%-1.35%), respectively., Conclusions: TN patients had the highest risk of LRR and the least benefit from PMRT; these patients may benefit from alternative treatment strategies. In contrast, in the era of HER2-directed therapy, the role of local therapy may need to be reassessed among HER2 patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Modern direct-acting anticoagulants are rapidly replacing vitamin K antagonists (VKA) in the management of millions of patients worldwide who require anticoagulation. These drugs include agents that inhibit activated factor X (FXa) (such as apixaban and rivaroxaban) or thrombin (such as dabigatran), and are collectively known today as non-VKA oral anticoagulants (NOACs). Since bleeding is the most common and most dangerous side effect of long-term anticoagulation, and because NOACs have very different mechanisms of action and pharmacokinetics compared with VKA, physicians are naturally concerned about the lack of experience regarding frequency, management and outcome of NOAC-associated bleeding in daily care. This review appraises trial and registry (or "real-world") data pertaining to bleeding complications in patients taking NOACs and VKA and provides practical recommendations for the management of acute bleeding situations.

It is of highest importance to find proteins responsible for breast cancer dissemination, for use as biomarkers or treatment targets. We established and performed a combined nontargeted LC-MS/MS and a targeted LC-SRM workflow for discovery and validation of protein biomarkers. Eighty breast tumors, stratified for estrogen receptor status and development of distant recurrence (DR ± ), were collected. After enrichment of N-glycosylated peptides, label-free LC-MS/MS was performed on each individual tumor in triplicate. In total, 1515 glycopeptides from 778 proteins were identified and used to create a map of the breast cancer N-glycosylated proteome. Based on this specific proteome map, we constructed a 92-plex targeted label-free LC-SRM panel. These proteins were quantified across samples by LC-SRM, resulting in 10 proteins consistently differentially regulated between DR+/DR- tumors. Five proteins were further validated in a separate cohort as prognostic biomarkers at the gene expression level. We also compared the LC-SRM results to clinically reported HER2 status, demonstrating its clinical accuracy. In conclusion, we demonstrate a combined mass spectrometry strategy, at large scale on clinical samples, leading to the identification and validation of five proteins as potential biomarkers for breast cancer recurrence. All MS data are available via ProteomeXchange and PASSEL with identifiers PXD001685 and PASS00643.

Globally, malignant melanoma shows a steady increase in the incidence among cancer diseases. Malignant melanoma represents a cancer type where currently no biomarker or diagnostics is available to identify disease stage, progression of disease or personalized medicine treatment. The aim of this study was to assess the tissue expression of alpha-synuclein, a protein implicated in several disease processes, in metastatic tissues from malignant melanoma patients. A targeted Selected Reaction Monitoring (SRM) assay was developed and utilized together with stable isotope labeling for the relative quantification of two target peptides of alpha-synuclein. Analysis of alpha-synuclein protein was then performed in ten metastatic tissue samples from the Lund Melanoma Biobank. The calibration curve using peak area ratio (heavy/light) versus concentration ratios showed linear regression over three orders of magnitude, for both of the selected target peptide sequences. In support of the measurements of specific protein expression levels, we also observed significant correlation between the protein and mRNA levels of alpha-synuclein in these tissues. Investigating levels of tissue alpha-synuclein may add novel aspect to biomarker development in melanoma, help to understand disease mechanisms and ultimately contribute to discriminate melanoma patients with different prognosis.

Malignant melanoma (MM) patients are being treated with an increasing number of personalized medicine (PM) drugs, several of which are small molecule drugs developed to treat patients with specific disease genotypes and phenotypes. In particular, the clinical application of protein kinase inhibitors has been highly effective for certain subsets of MM patients. Vemurafenib, a protein kinase inhibitor targeting BRAF-mutated protein, has shown significant efficacy in slowing disease progression. In this paper, we provide an overview of this new generation of targeted drugs, and demonstrate the first data on localization of PM drugs within tumor compartments. In this study, we have introduced MALDI-MS imaging to provide new information on one of the drugs currently used in the PM treatment of MM, vemurafenib. In a proof-of-concept in vitro study, MALDI-MS imaging was used to identify vemurafenib applied to metastatic lymph nodes tumors of subjects attending the regional hospital network of Southern Sweden. The paper provides evidence of BRAF overexpression in tumors isolated from MM patients and localization of the specific drug targeting BRAF, vemurafenib, using MS fragment ion signatures. Our ability to determine drug uptake at the target sites of directed therapy provides important opportunity for increasing our understanding about the mode of action of drug activity within the disease environment., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)