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The coronavirus disease-2019 (COVID-19) pandemic remains an extraordinary event that continues to strain healthcare systems worldwide. Unlike the military treatment facilities (MTFs) in the USA, which have ready access to tertiary care facilities, those MTFs in foreign countries confront a host of challenges in meeting mission requirements. In this article, we discuss the MTFs' COVID-19 response in the rural environment of Bavaria, Germany. Relevant factors including regional and clinic response, force health protection, and contingency planning, which influenced the MTFs response, are identified. These factors are further analyzed from a "lessons learned" perspective, and recommendations to shape the future response to a pandemic are provided. This current crisis portends a future where pandemics may remain an omnipresent threat. [ABSTRACT FROM AUTHOR]

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]

Intraoperative frozen section (FS) margin evaluation is not common practice for patients undergoing breast conservation therapy (BCT), but offers a significant reduction in reoperation. In this study, a technique to allow for more effective freezing of breast tissue was developed to perform FS evaluation of lumpectomy margins (FSM) for all patients undergoing BCT at an ambulatory surgery center. FS evaluation of sentinel lymph node biopsy specimens was performed concurrently. One hundred eighty-one study and 188 control patients, with and without FS evaluation, were compared. Reexcision was reduced 34% (from 48.9% to 14.9%) and reoperation was reduced 36% (from 55.3% to 19.3%) with FS evaluation. Most of the decrease in reoperative rate was because of a decrease in the need for margin reexcision. The number of patients requiring 1, 2, or 3 operations to complete therapy was 84, 92, and 12, respectively, in the control group, and 146, 33, and 2, respectively, in the study group. Lobular subtype, multifocal disease, and larger tumor size (≥2 cm) were significantly associated with failure of FSM to prevent reoperation, but reoperation rates were still significantly decreased in this subgroup of patients (from 75.5% to 43.8%) with FSM. This study highlights an innovative yet simple and adaptable FS approach that resulted in a nearly 3-fold reduction in reoperation for patients undergoing BCT. [ABSTRACT FROM AUTHOR]

Introduction: Population based studies (eg, Hershman et al. BCRT 2006 and Lohrisch et al. JCO 2006) showed poorer survival associated with long delays in adjuvant chemotherapy (CTX) initiation following definitive surgery (DS) for women with breast cancer (BC). Delays in CTX following diagnosis (DX) have not been evaluated. The ASCO/NCCN quality measures (QMs) recommend CTX <=120 days after DX for patients with stage II/III ER/PR negative disease. We sought to examine the impact of delayed CTX on survival overall and stratified by disease-specific prognostic factors. Methods: 4,608 women with stage I-III HER2 negative breast cancer diagnosed between 2000 and 2006 at 8 NCCN centers were identified using the NCCN outcomes database. Patients with T3/4 disease or who received neoadjuvant therapy were excluded. The association between CTX timing and OS was evaluated using multivariate Cox models adjusted for CTX type, age, race, BMI, residential distance, insurance, SES, comorbidity, ER/PR, LVI, grade, T stage, and N stage. The impact of CTX timing was evaluated using a >90-day (d) DS-to-CTX threshold, based on poor outcomes observed in prior studies, and a >120d DX-to-CTX threshold, based on the ASCO/NCCN QMs. Results: Median follow-up was 7.2 years and OS at 7 years was 89%. Overall, 401 (8.7%) patients received CTX >120d after DX and 113 (2.4%) patients received CTX >90d after DS. The DX-to-CTX interval was more strongly correlated with the DX-to-DS (r = 0.74) interval than DS-to-CTX (r = 0.54) interval. A >90d DS-to-CTX interval was significantly associated with poorer survival (HR: 1.65, 95% CI 1.04-2.60, p = 0.03) in adjusted analyses. Shorter DS-to-CTX thresholds of >60d (n = 636, HR: 1.13, 95% CI: 0.89-1.43, p = 0.319) or >75d (n = 273, HR: 1.05, 95% CI 0.74-1.49, p = 0.76) were not associated with OS. The association between a >120d DX-to-CTX interval and OS was not statistically significant (HR: 1.32, 95% CI 0.99-1.76, p = 0.06). Patients who received CTX >135d(n = 231, HR1.25, 95% CI: 0.87-1.81, p = 0.22)or>150d(n = 128, HR1.15, 95% CI: 0.59-2.24, p = 0.69) after DX did not display an increased risk of death. Excluding pathological staging factors from the model had no effect on the results. In subgroup analyses stratified by ER/PR, LVI, grade, T stage or N stage, a >120d delay in CTX did not display significant associations with OS. Among ER/PR negative patients, the association between a >120d delay and OS was borderline non-significant after adjusting the p-value for multiple hypothesis testing using the false discovery rate method (HR: 1.80, 95% CI: 1.16-2.79, p = 0.09). Conclusion: Consistent with previous studies, CTX delays of >90 days following surgery were associated with poorer survival. OS was not significantly compromised in patients with DX-to-CTX intervals >120 days although this analysis may have limited power to detect small effects. More variation in the DX-to-CTX interval was attributed to pre-surgery time which may explain the differences observed between the DX-to-CTX and DS-to-CTX intervals. Among patients with ER/PR negative disease, a non-significant association between OS and a >120 day DX-to -CTX interval was observed that warrants further examination. [ABSTRACT FROM AUTHOR]

Background: The results of the ACOSOG- Z0011 trial have had potential practice changing implications for the management of patients with positive sentinel lymph node (SLN) undergoing lumpectomy and radiation for breast cancer. However, some evidence suggests a shift in axillary management even prior to the initial report of data supporting sentinel lymph node biopsy (SLNB) alone in mid-2010. We analyzed data in the National Comprehensive Cancer Network (NCCN) outcomes database from NCCN centers and the Michigan Breast Oncology Quality Initiative (MiBOQI) hospitals to examine institutional practice patterns with respect to use of completion axillary dissection (CALND) for SLN positive breast cancer in the years leading up to publication of these trial results. We hypothesized that CALND would be omitted more frequently in women treated at NCCN centers compared to those treated at MiBOQI programs. Methods: We identified 2,172 women with clinical T1/T2 N0 breast cancer who underwent breast surgery and SLNB and had a positive SLN from 2007 through 2010 at one of 12 participating NCCN centers or 12 MiBOQI sites. Patient and tumor characteristics, definitive breast procedure, year of diagnosis, and institutional affiliation were analyzed as predictors of use of SLNB alone in univariate Chi-Square and multivariable logistic regression models. Results: CALND was omitted in 314 (14.5%) of the 2,172 patients. Over time, there was a dramatic increase in the use of SLNB alone (12% in 2007 to 23% in 2010). In the univariate analyses, increased patient age, later year of diagnosis, lower T stage, and lower pathologic N stage were significant predictors of use of SLNB alone (all p < .0001). There was no association between definitive breast surgery type, hormone receptor status, Her-2 Neu status, or institutional affiliation and use of SLNB alone. In the multivariable model, older age at diagnosis, later year of diagnosis, and lower pathologic N stage remained significant independent predictors of SLNB alone. There were no significant differences in rates of omission of CALND between NCCN and MIBOQI sites. Conclusions: Omission of CALND occurred frequently in women with SLN positive breast cancer cared for in both NCCN and MiBOQI institutions in advance of reporting results of ACOSOG-Z0011. This shift was seen in management of patients undergoing lumpectomy as well as mastectomy. Further study is warranted to determine the extent of durable practice changes as well as any impact on survival and local-regional control. [ABSTRACT FROM AUTHOR]

Background.--We sought to determine whether percutaneous core needle biopsy (CNB) of suspicious axillary lymph nodes in patients with breast cancer offers improved diagnostic accuracy compared with fine-needle aspiration (FNA). Methods.--Records of 400 patients were reviewed to identify patients undergoing ultrasound-guided biopsy followed by surgical axillary evaluation (sentinel lymph node biopsy or axillary lymph node dissection). Patients underwent diagnosis and treatment at a single high-volume county hospital. Data collected included demographics, treatment, biopsy, and surgical pathology. Percutaneous biopsy results were compared with results of sentinel lymph node biopsy or axillary lymph node dissection. Results.--Forty-seven patients met final study criteria. Twenty-two patients underwent FNA, and 25 underwent CNB. Sensitivity of FNA was 75% vs. 82% for CNB. Specificity for both was 100%. Additionally, a cost comparison of CNB versus FNA revealed CNB to be $404; FNA cost was $237. Conclusions.--The current data do not support the routine use of CNB over FNA for preoperative axillary staging in breast cancer patients with clinically negative axillas. Additionally, the substantial increase in cost without a marked improvement in sensitivity may favor the performance of FNA. [ABSTRACT FROM AUTHOR]

The article discusses research being done on breast cancer. It references a study being done by P. Gimbergues and colleagues published in the 2008 issue of "Annals of Surgical Oncology." It determines the clinicopathological factors that may influence the accuracy of sentinel lymph nodes biopsy after neoadjuvant chemotherapy for breast cancer.

The article discusses research being done on the use of diffuse optical spectroscopy (DOS) to predict response to neoadjuvant chemotherapy in breast cancer patients. It references a study by A. Cerussi and colleagues, published in the 2007 issue of "Proceedings of National Academy of Science USA." The study analyzed if DOS measurement can predict postsurgical pathological response. It discovered the sensitivity of DOS to tumor cellular metabolism. A comment on the study is also offered.

An abstract of the article "In Vivo Margin Assessment During Partial Mastectomy Breast Surgery Using Raman Spectroscopy," by A. S. Haka is presented.

The article discusses research being done on surgical procedures and predictors for successful breast-conserving surgery. It references a study by S. Loibl, G. von Minckwitz, G. Raab et al, published in the 2006 issue of the "Annals of Surgical Oncology." It was concluded that breast conservation after neoadjuvant chemotherapy is feasible in most patients with operable breast cancer.

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&lt;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 &lt; 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&#95;iss&#95;9&#95;7&#95;20190621&#95;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.)

Currently there are no clinically recognized molecular biomarkers for malignant melanoma (MM) for either diagnosing disease stage or measuring response to therapy. The aim of this feasibility study was to develop targeted selected reaction monitoring (SRM) assays for identifying candidate protein biomarkers in metastatic melanoma tissue lysate. In a pilot study applying the SRM assay, the tissue expression of nine selected proteins [complement 3 (C3), T-cell surface glycoprotein CD3 epsilon chain E (CD3E), dermatopontin, minichromosome maintenance complex component (MCM4), premelanosome protein (PMEL), S100 calcium binding protein A8 (S100A8), S100 calcium binding protein A13 (S100A13), transgelin-2 and S100B] was quantified in a small cohort of metastatic malignant melanoma patients. The SRM assay was developed using a TSQ Vantage triple quadrupole mass spectrometer that generated highly accurate peptide quantification. Repeated injection of internal standards spiked into matrix showed relative standard deviation (RSD) from 6% to 15%. All nine target proteins were identified in tumor lysate digests spiked with heavy peptide standards. The multiplex SRM peptide assay panel was then measured and quantified on a set of frozen MM tissue samples obtained from the Malignant Melanoma Biobank collected in Lund, Sweden. All nine proteins could be accurately quantified using the new SRM assay format. This study provides preliminary data on the heterogeneity of biomarker expression within MM patients. The S100B protein, which is clinically used as the pathology identifier of MM, was identified in 9 out of 10 MM tissue lysates. The use of the targeted SRM assay provides potential advancements in the diagnosis of MM that can aid in future assessments of disease in melanoma patients.

Background: The objectives and goals of the Southern Swedish Malignant Melanoma (SSMM) are to develop, build and utilize cutting edge biobanks and OMICS platforms to better understand disease pathology and drug mechanisms. The SSMM research team is a truly cross-functional group with members from oncology, surgery, bioinformatics, proteomics, and genomics initiatives. Within the research team there are members who daily diagnose patients with suspect melanomas, do follow-ups on malignant melanoma patients and remove primary or metastatic lesions by surgery. This inter-disciplinary clinical patient care ensures a competence build as well as a best practice procedure where the patient benefits., Methods: Clinical materials from patients before, during and after treatments with clinical end points are being collected. Tissue samples as well as bio-fluid samples such as blood fractions, plasma, serum and whole blood will be archived in 384-high density sample tube formats. Standardized approaches for patient selections, patient sampling, sample-processing and analysis platforms with dedicated protein assays and genomics platforms that will hold value for the research community are used. The patient biobank archives are fully automated with novel ultralow temperature biobank storage units and used as clinical resources., Results: An IT-infrastructure using a laboratory information management system (LIMS) has been established, that is the key interface for the research teams in order to share and explore data generated within the project. The cross-site data repository in Lund forms the basis for sample processing, together with biological samples in southern Sweden, including blood fractions and tumor tissues. Clinical registries are associated with the biobank materials, including pathology reports on disease diagnosis on the malignant melanoma (MM) patients., Conclusions: We provide data on the developments of protein profiling and targeted protein assays on isolated melanoma tumors, as well as reference blood standards that is used by the team members in the respective laboratories. These pilot data show biobank access and feasibility of performing quantitative proteomics in MM biobank repositories collected in southern Sweden. The scientific outcomes further strengthen the build of healthcare benefit in the complex challenges of malignant melanoma pathophysiology that is addressed by the novel personalized medicines entering the market.

Despite the low likelihood of malignancy, it is recommended that all women with pathologic nipple discharge undergo duct excision based on the inadequate sensitivity of diagnostic modalities. However, these data originates prior to recent improvements in breast imaging. We performed a retrospective review of patients evaluated in the setting of modern diagnostic breast imaging. Of 175 women referred to our breast clinic with a primary complaint of nipple discharge, 142 (81%) had suspicious discharge. Of the 23 patients who opted for observation over duct excision, with a mean follow-up of 3.3 years, none have been diagnosed with cancer. Among patients who proceeded with surgery, cancer was diagnosed in seven patients (5%). Six of the seven patients had either an abnormal mammogram or ultrasound. Among 46 patients with suspicious nipple discharge, a normal physical exam and normal diagnostic mammogram/ultrasound, only one malignancy (2%) was identified in a 79-year-old patient with a personal history of breast cancer. In selected patients with suspicious nipple discharge, but normal physical exam and diagnostic imaging, short-term observation with repeat evaluation seems reasonable for patients who do not desire duct excision., (© 2011 Wiley Periodicals, Inc.)

Background: The actual impact of emergency department (ED) 'wait' time on hospital mortality in patients admitted as a medical emergency has often been debated. We have evaluated the impact of such waits on 30-day mortality, for all medical patients over a 7-year period., Methods: All patients admitted as medical emergencies by the ED between 2002 and 2008 were studied; we looked at the impact of time to medical referral and subsequent time to a ward bed on any inhospital death within 30 days. Significant univariate predictors of outcome, including Charlson's comorbidity and acute illness severity score, were entered into a multivariate regression model, adjusting the univariate estimates of the readmission status on mortality., Results: We studied 23 114 consecutive acute medical admissions between 2002 and 2008. The triage category in the ED was highly predictive of subsequent 30-day mortality ranging from 4.8 (category 5) to 46.1% (category 1). After adjustment for all outcome predictors, including comorbidity and illness severity, both door-to-team and team-to-ward times were independent predictors of death within 30 days with respective odds ratios of 1.13 (95% confidence interval 1.07-1.18), and 1.07 (95% confidence interval 1.02-1.13)., Conclusion: Delay to admission have been shown to be independently adversely related to mortality outcome. We recommend maximal target limits of 4 and 6 h for referrals and admissions, respectively, based on these mortality observations.

Objectives: Stress levels among staff in the Mater Misericordiae University Hospital Emergency Department were studied by questionnaire in 2000, which demonstrated a high level of self reported stress. The aim of this study was to ascertain if stress levels had reduced following changes in the department., Method: The study was repeated using the same questionnaire in 2006, after changes had occurred., Results: There was a significant reduction in the percentage of staff that reported they were under severe or unbearable stress, from 37% in 2000 to 10% in 2006 (p = 0.002). A total of 60% felt the social environment of their work was satisfactory in 2006 compared to 40% in 2000 (p = 0.03). Compared to 2000, a significantly lower proportion reported they had a low degree of control over their job, and a significantly higher proportion reported a medium level of control over their job in 2006 (p = 0.03)., Conclusions: Compared with the results of the previous study, reported stress levels have reduced overall, which coincided with a significant increase in staffing levels in the department.

Objectives: The Needlecatcher comprises a tissue forceps at one end, with a 'piston and barrel' system, which acts as a needle grasper, at the other end of the instrument. It minimizes exposure of the needle during suturing, potentially reducing risk of injury. We evaluate its effect on operator safety during simple wound closure., Methods: Video analysis of 10 clinicians (six junior doctors and four advanced nurse practitioners) closing a standard simulated wound using their normal technique was performed. They were trained in the use of the Needlecatcher, and used it for 10 weeks closing simple wounds in the Emergency Department. Video analysis of wound closure was repeated, using the new instrument. Clinicians filled out a questionnaire for each episode of wound closure, which assessed how they perceived their safety was affected by the device., Results: Video analysis of clinicians showed that the needle was secured in an instrument and thus unexposed for an average of 60% of the duration of the procedure by standard technique, compared with 95% using the Needlecatcher, with a change of 35% [95% confidence interval (CI): 14-58%, P = 0.005]. Episodes where the needle was grasped by an operator's finger were reduced by 50% (95% CI: 15-85%, P = 0.028). In the questionnaire study of 53 episodes of wound closure, operators perceived their safety to be increased in 38 (71.7%, 95% CI: 66.2-77.2%) episodes, were neutral in 10, and felt their safety was reduced in five., Conclusion: The Needlecatcher showed the potential to reduce the risk of needlestick injury while suturing.

The aim of this study was to investigate a relationship between FVL-mutation and levels of haemoglobin (Hb) in patients with venous thromboembolism (VTE). From March 1998 to December 2005, 927 consecutive patients with objectively diagnosed VTE were registered in the Malmö Thrombophilia Study (MATS). Female patients with FVL-mutation below 50 years of age had significantly higher median-Hb (133 vs. 126 g/l; P < 0.001) compared to female patients below the age of 50 years without FVL. No significant difference could be found for men or women above 50 years of age or men below 50 years of age. Female patients below the age of 50 years with FVL-mutation and VTE are associated with higher median Hb, and this finding is in accordance with earlier hypothesis that FVL-mutation may have constituted an evolutionary selection advantage.