Global consensus statement on simulation-based practice in healthcare.

Simulation plays a pivotal role in addressing universal healthcare challenges, reducing education inequities, and improving mortality, morbidity and patient experiences. It enhances healthcare processes and systems, contributing significantly to the development of a safety culture within organizations. It has proven to be cost-effective and successful in enhancing team performance, fostering workforce resilience and improving patient outcomes.Through an international collaborative effort, an iterative consultation process was conducted with 50 societies operating across 67 countries within six continents. This process revealed common healthcare challenges and simulation practices worldwide. The intended audience for this statement includes policymakers, healthcare organization leaders, health education institutions, and simulation practitioners. It aims to establish a consensus on the key priorities for the broad adoption of exemplary simulation practice that benefits patients and healthcare workforces globally.Key recommendations Advocating for the benefits that simulation provides to patients, staff and organizations is crucial, as well as promoting its adoption and integration into daily learning and practice throughout the healthcare spectrum. Low-cost, high-impact simulation methods should be leveraged to expand global accessibility and integrate into system improvement processes as well as undergraduate and postgraduate curricula. Support at institutional and governmental level is essential, necessitating a unified and concerted approach in terms of political, strategic and financial commitment.It is imperative that simulation is used appropriately, employing evidence-based quality assurance approaches that adhere to recognized standards of best practice. These standards include faculty development, evaluation, accrediting, credentialing, and certification.We must endeavor to provide equitable and sustainable access to high-quality, contextually relevant simulation-based learning opportunities, firmly upholding the principles of equity, diversity and inclusion. This should be complemented with a renewed emphasis on research and scholarship in this field.Call for action We urge policymakers and leaders to formally acknowledge and embrace the benefits of simulation in healthcare practice and education. This includes a commitment to sustained support and a mandate for the application of simulation within education, training, and clinical environments.We advocate for healthcare systems and education institutions to commit themselves to the goal of high-quality healthcare and improved patient outcomes. This commitment should encompass the promotion and resource support of simulation-based learning opportunities for individuals and interprofessional teams throughout all stages and levels of a caregiver's career, in alignment with best practice standards.We call upon simulation practitioners to champion healthcare simulation as an indispensable learning tool, adhere to best practice standards, maintain a commitment to lifelong learning, and persist in their fervent advocacy for patient safety.This statement, the result of an international collaborative effort, aims to establish a consensus on the key priorities for the broad adoption of exemplary simulation practice that benefits patients and healthcare workforces globally.

Factors associated with practice readiness among newly qualified nurses in their first two years of practice.

BACKGROUND: Newly graduated nurses undergo stress and role adjustment as they transition into practice during the first year and continue to struggle beyond the first year. Determining their practice readiness can aid in the development of interventions to facilitate workplace readiness for nurses in their first two years entering the nursing profession. OBJECTIVES: To examine (i) extent of practice readiness of new nurses in their role; and (ii) associations between nurses' practice readiness and demographic and occupational variables, and reasons for choosing nursing profession. DESIGN: A cross-sectional study. SETTINGS AND PARTICIPANTS: A total of 445 registered nurses who graduated within the last two years and working in an academic medical centre in Singapore. METHODS: Participants completed an online questionnaire with questions from Casey-Fink Readiness for Practice Survey and questions related to key competencies for future practice. RESULTS: More than half (57.5 %) identified at least three skills and procedures which they were uncomfortable performing independently as they transition into the clinical practice, including: (i) responding to emergency (ii) tracheostomy care; and (iii) chest tube care. The top three reasons for choosing nursing as a career were: (i) nursing is a stable industry (54.2 %); (ii) I want to help people (52.1 %); and (iii) able to work anywhere in the world (44.3 %). Nurses were most concerned with areas of trials and tribulations (42.5 %) and clinical competency (36.6 %). When compared to nurses in their first-year post-graduation, those working in their second year reported more confidence in the ability to problem solve (p = 0.003), care for a person who is dying (p = 0.004), and less difficulties in prioritizing care needs (p = 0.04). They also perceived themselves as a good problem solver (p = 0.03). CONCLUSIONS: It is critical to continue supporting nurses' practice readiness beyond their first year of practice in their confidence and development of skills of higher complexity.

Cancer Metastasis and Treatment Resistance: Mechanistic Insights and Therapeutic Targeting of Cancer Stem Cells and the Tumor Microenvironment.

Cancer metastasis and treatment resistance are the main causes of treatment failure and cancer-related deaths. Their underlying mechanisms remain to be fully elucidated and have been attributed to the presence of cancer stem cells (CSCs)-a small population of highly tumorigenic cancer cells with pluripotency and self-renewal properties, at the apex of a cellular hierarchy. CSCs drive metastasis and treatment resistance and are sustained by a dynamic tumor microenvironment (TME). Numerous pathways mediate communication between CSCs and/or the surrounding TME. These include a paracrine renin-angiotensin system and its convergent signaling pathways, the immune system, and other signaling pathways including the Notch, Wnt/ß-catenin, and Sonic Hedgehog pathways. Appreciation of the mechanisms underlying metastasis and treatment resistance, and the pathways that regulate CSCs and the TME, is essential for developing a durable treatment for cancer. Pre-clinical and clinical studies exploring single-point modulation of the pathways regulating CSCs and the surrounding TME, have yielded partial and sometimes negative results. This may be explained by the presence of uninhibited alternative signaling pathways. An effective treatment of cancer may require a multi-target strategy with multi-step inhibition of signaling pathways that regulate CSCs and the TME, in lieu of the long-standing pursuit of a 'silver-bullet' single-target approach.

Effective disinfecting of protective devices used in the course of treating SARS-CoV2-positive patients.

BACKGROUND: Powered Air-Purifying Respirator (PAPR) was widely used in Sengkang General Hospital (SKH) during the SARS-CoV-2 outbreak. Ensuring a sustained supply of clean and reusable PAPR masks for frontline medical team is an immediate challenge. The Central Sterile Supplies Unit (CSSU) adopts existing disinfection methods and technology for the reprocessing of reusable personal protective equipment (PPE) such as PAPR masks and goggles. OBJECTIVE: To determine an effective disinfecting method for protective devices used in the course of treating SARS-CoV2-positive patients. METHOD: A comparison on surface disinfection and modified thermal disinfection outcome was conducted on 30 PAPR masks through detecting the presence of adenosine triphosphate (ATP) by swab following both disinfecting methods. RESULTS: The modified thermal cycles emerged as the recommended disinfection method. DISCUSSION: The outcome of this study has enhanced understanding on the risk imposed on frontline healthcare personnel who perform surface disinfecting on masks for reuse during the work shift. Leveraging on the current expertise from existing instrument logistics, CSSU takes charge of the processing and stock management of SKH's PAPR masks. An additional workflow is needed to establish reprocessing methods for other reusable PPEs such as face shields or overalls.

ß-blocker therapy for infantile hemangioma.

INTRODUCTION: Fifteen percent of proliferating infantile hemangioma (IH) require intervention because of the threat to function or life, ulceration, or tissue distortion. Propranolol is the mainstay treatment for problematic proliferating IH. Other ß-blockers and angiotensin-converting enzyme (ACE) inhibitors have been explored as alternative treatments. AREAS COVERED: The demonstration of a hemogenic endothelium origin of IH, with a neural crest phenotype and multi-lineage differentiation capacity, regulated by the renin-angiotensin system, underscores its programmed biologic behavior and accelerated involution induced by propranolol, other ß-blockers and ACE inhibitors. We review the indications, dosing regimens, duration of treatment, efficacy and adverse effects of propranolol, and therapeutic alternatives including oral atenolol, acebutolol, nadolol, intralesional propranolol injections, topical propranolol and timolol, and oral captopril. EXPERT OPINION: Improved understanding of the biology of IH provides insights into the mechanism of action underscoring its accelerated involution induced by propranolol, other ß-blockers and ACE inhibitors. More research is required to understand the optimal dosing and duration, efficacy and safety of these alternative therapies. Recent demonstration of propranolol's actions mediated by non-ß-adrenergic isomer R-propranolol on stem cells, offers an immense opportunity to harness the efficacy of ß-blockers to induce accelerated involution of IH, while mitigating their ß-adrenergic receptor-mediated adverse effects.

Cancer stem cell subpopulations in moderately differentiated head and neck cutaneous squamous cell carcinoma.

Cancer stem cells (CSC), the putative origin of cancer, account for local recurrence and metastasis. We aimed to identify and characterize CSCs within moderately differentiated head and neck cutaneous squamous cell carcinoma (MDHNCSCC). Formalin-fixed paraffin-embedded MDHNCSCC sections of ten patients underwent 3,3-diaminobenzidine (DAB) immunohistochemical (IHC) staining for induced pluripotent stem cell (iPSC) markers OCT4, NANOG, SOX2, KLF4 and c-MYC. Localization of these markers was investigated using immunofluorescence (IF) IHC staining of three of these MDHNCSCC samples. mRNA expression of these iPSC markers in the MDHNCSCC tissue samples was determined by colorimetric in-situ hybridization (CISH, n = 6), and reverse-transcription quantitative polymerase chain reaction (RT-qPCR, n = 4). RT-qPCR was also performed on four MDHNCSCC-derived primary cell lines. DAB IHC staining demonstrated expression of all five iPSC markers within all ten MDHNCSCC tissues samples. CISH and RT-qPCR confirmed mRNA expression of all five iPSC markers within all MDHNCSCC tissues samples examined. RT-PCR demonstrated mRNA transcripts of all five iPSC markers in all four MDHNCSCC-derived primary cell lines. IF IHC staining showed co-expression of OCT4 with SOX2 and KLF4 throughout the tumor nests (TNs) and peri-tumoral stroma (PTS). There was an OCT4+/NANOG+ subpopulation within the TNs, and an OCT4+/NANOG- subpopulation and an OCT4+/NANOG+ subpopulation within the PTS. All iPSC markers were expressed by the endothelium of microvessels within the PTS. Our findings suggest the presence of an OCT4+/NANOG+/SOX2+/KLF4+/c-MYC+ CSC subpopulation within the TNs, PTS and endothelium of microvessels within the PTS; and an OCT4+/NANOG-/SOX2+/KLF4+/c-MYC+ subpopulation exclusively within the PTS in MDHNCSCC. These CSC subpopulations could be a potential novel therapeutic target for treatment of MDHNCSCC.

Embryonic Stem Cell-Like Population in Dupuytren's Disease Expresses Components of the Renin-Angiotensin System.

The renin-angiotensin system (RAS) mediates cardiac and renal fibrosis. Dupuytren's disease (DD) is a proliferative fibromatosis affecting the hands. This study investigated the expression of the RAS in DD. METHODS: 3,3-Diaminobenzidine (DAB) and immunofluorescent immunohistochemical (IHC) staining for (pro)renin receptor (PRR), angiotensin-converting enzyme (ACE), angiotensin II receptor 1 (ATIIR1), and angiotensin II receptor 2 (ATIIR2) was performed on 4-µm thick formalin-fixed paraffin-embedded sections of DD cords and nodules from 6 patients. Western blotting (WB) and NanoString mRNA analysis were performed to confirm RAS protein expression and transcriptional activation, respectively. RESULTS: IHC staining demonstrated the expression of PRR, ACE, ATIIR1, and ATIIR2 on the ERG+ and CD34+ endothelium of the micro vessels surrounding the DD cords and nodules. PRR was also expressed on the pericyte layer of these microvessels. WB confirmed protein expression of PRR, ACE, and ATIIR2 but not ATIIR1. NanoString analysis confirmed transcriptional activation of PRR, ACE, ATIIR1, but ATIIR2 was below detectable levels. CONCLUSIONS: We demonstrated expression of PRR, ATIIR1, ATIIR2, and ACE on the embryonic stem cell-like cell population on the microvessels surrounding DD nodules and cords by IHC staining, although the expression of ATIIR1 was not confirmed by WB and that of ATIIR2 was below detectable levels on NanoString analysis. These findings suggest the embryonic stem cell-like cell population as a potential therapeutic target for DD, by using RAS modulators.

Expression of Cathepsins B, D, and G in Isocitrate Dehydrogenase-Wildtype Glioblastoma.

AIM: To investigate the expression of cathepsins B, D, and G, in relation to the cancer stem cell (CSC) subpopulations, we have previously characterized within isocitrate dehydogenase (IDH)-wildtype glioblastoma (IDHWGB). METHODS: 3,3-Diaminobezidine (DAB) immunohistochemical (IHC) staining for cathepsins B, D, and G, was performed on 4µm-thick formalin-fixed paraffin-embedded IDHWGB samples obtained from six patients. Two representative DHWGB samples from the original cohort of patients were selected for immunofluorescent (IF) IHC staining, to identify the localization of the cathepsins in relation to the CSC subpopulations. NanoString gene expression analysis and colorimetric in situ hybridization (CISH) were conducted to investigate the transcriptional activation of genes encoding for cathepsins B, D, and G. Data obtained from cell counting of DAB IHC-stained slides and from NanoString analysis were subjected to statistical analyses to determine significance. RESULTS: Cathepsin B and cathepsin D were detected in IDHWGB by DAB IHC staining. IF IHC staining demonstrated the expression of both cathepsin B and cathepsin D by the OCT4+ and SALL4+ CSC subpopulations. NanoString gene analysis and CISH confirmed the abundant transcript expression of these cathepsins. The transcriptional and translational expressions of cathepsin G were minimal and were confined to cells within the microvasculature. CONCLUSION: This study demonstrated the expression of cathepsin B and cathepsin D but not cathepsin G within the CSC subpopulations of IDHWGB at both the transcriptional and translational level. Cathepsin G was expressed at low levels and was not localized to the CSC population of IDHWGB. The novel finding of cathepsin B and cathepsin D in IDHWGB suggests the presence of bypass loops for the renin-angiotensin system, which may facilitate the production of angiotensin peptides. Elucidating the precise role of these cathepsins may lead to better understanding and more effective treatment of this aggressive tumor.

Embryonic Stem Cell-like Population in Dupuytren's Disease.

BACKGROUND: Recent research has identified mesenchymal stem cells (MSCs) within Dupuytren's disease (DD) tissue and they have been proposed to give rise to the myofibroblasts, implicated in the progression of this condition. The aim of this study was to identify and characterize the primitive population that might be upstream of the MSC population, within DD. METHODS: Formalin-fixed paraffin-embedded 4-µm-thick sections of DD cords and nodules obtained from 6 patients underwent 3,3-diaminobenzidine and immunofluorescent immunohistochemical staining for embryonic stem cell (ESC) markers OCT4, NANOG, SOX2, pSTAT3, and SALL4 and endothelial markers CD34 and ERG. NanoString gene expression analysis was performed to determine the transcriptional activation of these markers. RESULTS: Immunohistochemical staining demonstrated the expression of ESC markers OCT4, NANOG, SOX2, pSTAT3, and SALL4 on the endothelium of the microvessels expressing CD34 and ERG, particularly those surrounding the DD nodules. NanoString analysis confirmed the transcriptional activation of OCT4, NANOG, STAT3, and SALL4, but not SOX2. CONCLUSION: This article demonstrates the novel finding of an ESC-like population expressing ESC markers OCT4, NANOG, SOX2, pSTAT3, and SALL4, localized to the endothelium of the microvessels within DD tissue, suggesting a potential therapeutic target for this condition.