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Rationale: Clinical deterioration of patients hospitalized outside the ICU is a source of potentially reversible morbidity and mortality. To address this, some acute care hospitals have implemented systems aimed at detecting and responding to such patients., Objectives: To provide evidence-based recommendations for hospital clinicians and administrators to optimize recognition and response to clinical deterioration in non-ICU patients., Panel Design: The 25-member panel included representatives from medicine, nursing, respiratory therapy, pharmacy, patient/family partners, and clinician-methodologists with expertise in developing evidence-based Clinical Practice Guidelines., Methods: We generated actionable questions using the Population, Intervention, Control, and Outcomes (PICO) format and performed a systematic review of the literature to identify and synthesize the best available evidence. We used the Grading of Recommendations Assessment, Development, and Evaluation Approach to determine certainty in the evidence and to formulate recommendations and good practice statements (GPSs)., Results: The panel issued 10 statements on recognizing and responding to non-ICU patients with critical illness. Healthcare personnel and institutions should ensure that all vital sign acquisition is timely and accurate (GPS). We make no recommendation on the use of continuous vital sign monitoring among unselected patients. We suggest focused education for bedside clinicians in signs of clinical deterioration, and we also suggest that patient/family/care partners' concerns be included in decisions to obtain additional opinions and help (both conditional recommendations). We recommend hospital-wide deployment of a rapid response team or medical emergency team (RRT/MET) with explicit activation criteria (strong recommendation). We make no recommendation about RRT/MET professional composition or inclusion of palliative care members on the responding team but suggest that the skill set of responders should include eliciting patients' goals of care (conditional recommendation). Finally, quality improvement processes should be part of a rapid response system., Conclusions: The panel provided guidance to inform clinicians and administrators on effective processes to improve the care of patients at-risk for developing critical illness outside the ICU., Competing Interests: Funding for these guidelines was provided solely by the Society of Critical Care Medicine. Panel members disclosed all potential financial and intellectual conflicts of interest according to the American College of Critical Care Medicine/Society of Critical Care Medicine Standard Operating Procedures. Refer to Supplemental Digital Contents 1 and 2 (http://links.lww.com/CCM/H434) for details. Dr. Penoyer received funding from Ivenix, Inc, Avanos, ICU Medical, and BD. Dr. Davis disclosed he is a consultant for Zoll and Healthstream and is Chief Executive Officer of Medical X Technologies. Dr. Edelson disclosed that she is president and co-founder of AgileMD and received equity interest, she is an employee of the National Institutes of Health, and received a research grant from BARDA (ARCD.P0535US). Dr. Rowley received funding from Draeger, STIMIT, and Vyaire. Dr. DeVita disclosed that he is a consultant for Hill Rom. Dr. Welch disclosed that he is an advisor in a one-off Becton, Dickinson and Co. Adult and Specialist Critical Care Advisory Board. Dr. Kellett disclosed that he is the founder and major shareholder of Tapa Healthcare DAC. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

We report a case of a 62-year-old woman with a decade-long history of atypical chest pain resulting in a largely negative cardiac workup, who developed significant angiographically demonstrated coronary vasospasm thought to be due to a small dose of intravenous ketamine. In patients with a history of atypical chest pain despite a reassuring cardiac evaluation, providers should carefully consider medications that may precipitate coronary vasospasm and be prepared to treat it accordingly., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Rationale: Clinical deterioration of patients hospitalized outside the ICU is a source of potentially reversible morbidity and mortality. To address this, some acute care facilities have implemented systems aimed at detecting and responding to such patients., Objectives: To provide evidence-based recommendations for hospital clinicians and administrators to optimize recognition and response to clinical deterioration in non-ICU patients., Panel Design: The 25-member panel included representatives from medicine, nursing, respiratory therapy, pharmacy, patient/family partners, and clinician-methodologists with expertise in developing evidence-based clinical practice guidelines., Methods: We generated actionable questions using the Population, Intervention, Control, and Outcomes format and performed a systematic review of the literature to identify and synthesize the best available evidence. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to determine certainty in the evidence and to formulate recommendations and good practice statements (GPSs)., Results: The panel issued 10 statements on recognizing and responding to non-ICU patients with critical illness. Healthcare personnel and institutions should ensure that all vital sign acquisition is timely and accurate (GPS). We make no recommendation on the use of continuous vital sign monitoring among "unselected" patients due to the absence of data regarding the benefit and the potential harms of false positive alarms, the risk of alarm fatigue, and cost. We suggest focused education for bedside clinicians in signs of clinical deterioration, and we also suggest that patient/family/care partners' concerns be included in decisions to obtain additional opinions and help (both conditional recommendations). We recommend hospital-wide deployment of a rapid response team or medical emergency team (RRT/MET) with explicit activation criteria (strong recommendation). We make no recommendation about RRT/MET professional composition or inclusion of palliative care members on the responding team but suggest that the skill set of responders should include eliciting patients' goals of care (conditional recommendation). Finally, quality improvement processes should be part of a rapid response system (GPS)., Conclusions: The panel provided guidance to inform clinicians and administrators on effective processes to improve the care of patients at-risk for developing critical illness outside the ICU., Competing Interests: Panel members disclosed all potential financial and intellectual conflicts of interest according to the American College of Critical Care Medicine/Society of Critical Care Medicine Standard Operating Procedures. For details, please refer to Supplemental Digital Contents 1 and 2 (http://links.lww.com/CCM/H433). Dr. Penoyer received funding from Ivenix, Avanos, ICU Medical, and BD. Dr. Davis disclosed he is a consultant for Zoll and Healthstream and is Chief Executive Officer of Medical X Technologies. Dr. Edelson disclosed that she is president and co-founder of AgileMD and received equity interest, she is an employee of the National Institutes of Health, and she received a research grant from BARDA (ARCD.P0535US). Dr. Rowley received funding from Draeger, STIMIT, and Vyaire. Dr. DeVita disclosed that he is a consultant for Hill Rom. Dr. Welch disclosed that he is an advisor in a one-off Becton, Dickinson and Co. Adult and Specialist Critical Care Advisory Board. Dr. Kellett disclosed that he is the founder and major shareholder of Tapa Healthcare DAC. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Emergency intubations are commonly associated with adverse events when performed in critically ill patients. A detailed look at intubation factors and their association with procedural success and mortality has yet to be fully conducted., Methods: A total of 299 successive intubations at a tertiary Veteran Affair hospital were analyzed. Situational factors, personnel involved, intubation indications, induction agents, and airway management techniques were prospectively collected and entered into univariable and multivariable analyses to identify factors associated with procedural difficulty and mortality., Results: The use of paralytics was associated with easier intubations (OR: 0.31, 95% CI: 0.11-0.87, p = .03). The use of direct laryngoscopy or video laryngoscopy had no significant association with difficult intubation. Factors associated with increased 30-day mortality were cardiac arrest (OR: 7.90, 95% CI: 2.77-22.50, p < .001), hypoxia as indication for intubation (OR: 2.31, 95% CI: 1.23-4.35, p = .009), and nadir SpO 2  < 90% (OR: 2.70, 95% CI: 1.01-7.21, p = .048). Presence of an attending anesthesiologist during intubation was associated with a lower 30-day mortality (OR: 0.11, 95% CI: 0.04-0.29, p < .001). Factors associated with increased 90-day mortality were cardiac arrest (OR: 6.57, 95% CI: 2.23-19.34, p = .001), hypoxia as indication for intubation (OR: 1.97, 95% CI: 1.10-3.55, p = .023), and older age (OR: 1.38, 95% CI: 1.07-1.78, p = .013). Similarly, presence of an attending anesthesiologist was found to be associated with a lower 90-day mortality (OR: 0.19, 95% CI: 0.07-0.50, p = .001)., Conclusion: Cardiovascular and respiratory instability were associated with increased 30- and 90-day mortality. Presence of an attending anesthesiologist was associated with a better survival following intubation outside operating room., (© 2023 Acta Anaesthesiologica Scandinavica Foundation.)

Introduction Point-of-care ultrasound (POCUS) has become an integral asset in intensive care units (ICUs). However, there is limited literature on the value of POCUS in evaluating deteriorating patients outside the ICU. In this study, we sought to investigate the use and impact of POCUS by ICU triage teams in hospitals outside of the ICU setting. Methods ICU triage fellows were provided a portable ultrasound to use as part of their evaluations during consultations and hospital code activations. Fellows were asked to fill out a survey on how ultrasound was used and its impact on patient management. Free-text data such as reason for ultrasound use, views obtained, clinical impressions before and after ultrasound, and clinical actions were recorded. These data were transcribed and categorized electronically. Results A total of 51 total resuscitations were documented. The most common reason for ICU triage team evaluation was hypotension (53%, N=27). The most common clinical focus for ultrasound use was cardiac assessment (53%, N=27), followed by volume status assessment (35%, N=18). The most common ultrasound views per encounter obtained were parasternal long (82%, N=42), followed by apical four-chamber view (76%, N=39) and subcostal view (75%, N=38). Out of 38 encounters with clinical impressions documented, 79% (N=30) of pre-ultrasound clinical impressions were confirmed by ultrasound use. Of total encounters, 35% (N=18) had a significant clinical action taken based on ultrasound findings (fluid resuscitation, vasopressor initiation, etc.). Conclusions Ultrasound is a valuable tool for patient evaluation in non-ICU wards, especially in confirming clinical impressions and guiding therapeutic actions. Some limitations of this study include reporting bias and incomplete capture of ultrasound use in non-ICU wards., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Gupta et al.)

Objectives: Physiological decompensation of hospitalized patients is common and is associated with substantial morbidity and mortality. Research surrounding patient decompensation has been hampered by the absence of a robust definition of decompensation and lack of standardized clinical criteria with which to identify patients who have decompensated. We aimed to: 1) develop a consensus definition of physiological decompensation and 2) to develop clinical criteria to identify patients who have decompensated., Design: We utilized a three-phase, modified electronic Delphi (eDelphi) process, followed by a discussion round to generate consensus on the definition of physiological decompensation and on criteria to identify decompensation. We then validated the criteria using a retrospective cohort study of adult patients admitted to the Hospital of the University of Pennsylvania., Setting: Quaternary academic medical center., Patients: Adult patients admitted to the Hospital of the University of Pennsylvania who had triggered a rapid response team (RRT) response between January 1, 2019, and December 31, 2020., Interventions: None., Measurements and Main Results: Sixty-nine experts participated in the eDelphi. Participation was high across the three survey rounds (first round: 93%, second round: 94%, and third round: 98%). The expert panel arrived at a consensus definition of physiological decompensation, "An acute worsening of a patient's clinical status that poses a substantial increase to an individual's short-term risk of death or serious harm." Consensus was also reached on criteria for physiological decompensation. Invasive mechanical ventilation, severe hypoxemia, and use of vasopressor or inotrope medication were bundled as criteria for our novel decompensation metric: the adult inpatient decompensation event (AIDE). Patients who met greater than one AIDE criteria within 24 hours of an RRT call had increased adjusted odds of 7-day mortality (adjusted odds ratio [aOR], 4.1 [95% CI, 2.5-6.7]) and intensive care unit transfer (aOR, 20.6 [95% CI, 14.2-30.0])., Conclusions: Through the eDelphi process, we have reached a consensus definition of physiological decompensation and proposed clinical criteria with which to identify patients who have decompensated using data easily available from the electronic medical record, the AIDE criteria., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Rapid response systems (RRSs) are used in hospitals to identify and treat deteriorating patients. However, RRS implementation and outcomes in orthopedic and surgical patients remain controversial. We aimed to investigate whether the RRS affects mortality and complications after orthopedic surgery. Methods: The National Health Insurance Service of South Korea provided the data for this population-based cohort study. Individuals who were admitted to the hospital that implemented RRS were categorized into the RRS group and those admitted to a hospital that did not implement the RRS were categorized into the non-RRS group. In-hospital mortality and postoperative complications were the endpoints. Results: A total of 931,774 adult patients were included. Among them, 93,293 patients underwent orthopedic surgery in a hospital that implemented RRS and were assigned to the RRS group, whereas 838,481 patients were assigned to the non-RRS group. In multivariable logistic regression analysis, the RRS group was not associated with in-hospital mortality after orthopedic surgery compared with the non-RRS group (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.80, 1.08; P = 0.350). However, the RRS group was associated with a 14% lower postoperative complication rate after orthopedic surgery than the non-RRS group (OR 0.86, 95% CI 0.84, 0.86; P < 0.001). Conclusions: The RRS was not associated with in-hospital mortality following orthopedic surgery in South Korea. However, RRS deployment was related to a decreased risk of postoperative complications in patients undergoing orthopedic surgery. [ABSTRACT FROM AUTHOR]

Point-of-care ultrasound (POCUS) is emerging as a valuable adjunct tool to medical history and physical examination, enhancing the diagnosis and management of diseases. Even though it was initially concentrated in intensive care units and emergency departments, its application has now expanded to various medical specialties, including nephrology. Point-ofcare ultrasound has become very useful in the assessment of native and graft kidneys, arteriovenous access assessment, procedural guidance, and the objective evaluation of volume status, which sometimes might be clinically difficult. Notably, it has been quite useful in volume assessment in patients with chronic liver disease and acute kidney injury. The incorporation of POCUS into nephrology education and practice has gained a momentum, and Portugal has set a good example. Despite its various challenges and limitations, as a group of young nephrologists, we believe that a structured training program for POCUS is needed, which will culminate in its wide adoption in daily practice. [ABSTRACT FROM AUTHOR]

Background: Although progress has been made in identifying and responding to acutely deteriorating ward patients, judgements about the level of care required for patients after medical emergency team review are complex, rarely including a formal assessment of illness severity. This challenges staff and resource management practices and patient safety., Objective: This study sought to quantify the illness severity of ward patients after medical emergency team review., Research Design and Setting: This retrospective cohort study examined the clinical records of 1500 randomly sampled adult ward patients following medical emergency team review at a metropolitan tertiary hospital. Outcome measures were the derivation of patient acuity and dependency scores using sequential organ failure assessment and nursing activities score instruments. Findings are reported using the STROBE guideline for cohort studies., No Patient or Public Contribution: No direct patient contact was made during the data collection and analysis phases of the study., Results: Patients were male (52.6%), unplanned (73.9%) medical admissions (57.5%), median age of 67 years. The median sequential organ failure assessment score was 4% and 20% of patients demonstrated multiple organ system failure requiring non typical monitoring and coordination arrangements for at least 24 h. The median nursing activities score was 86% suggestive of a near 1:1 nurse-to-patient ratio. More than half of all patients required enhanced levels of assistance with mobilization (58.8%) and hygiene (53.9%) activities., Conclusions: Patients who remain on the ward following medical emergency team review had complex combinations of organ dysfunction, with levels of dependency similar to those found in intensive care units. This has implications for ward and patient safety and continuity of care arrangements., Relevance to Clinical Practice: Profiling illness severity at the conclusion of the medical emergency team review may help determine the need for special resource and staffing arrangements or placement within the ward environment., (© 2023 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

Aim: To explore general ward nurses' attitudes and perceptions towards recognising and responding to clinical deterioration in a hospital with automated rapid response system activation., Background: There is growing interest in deploying automated clinical deterioration notification systems to reduce delayed or failed recognition and response to clinical deterioration of ward patients. However, little is known about its impact on ward nurses' perspectives and work patterns., Design: A mixed-methods study., Methods: Online survey of 168 registered nurses and individual interviews with 10 registered nurses in one acute hospital in Singapore. The study adhered to the STROBE checklist for cross-sectional studies and the COREQ guidelines for qualitative studies., Results: Many nurses (38.1%) rarely performed patient assessments or observations other than vital signs assessment to assess for early signs of clinical deterioration. About 30% were worried about being criticised for calling the primary team doctors. Four themes emerged from the qualitative analysis: automated rapid response system activation as a safety net, being more cautious with vital signs monitoring, the NEWS2 alone is inadequate, and ward nurses as the 'middleman' between the intensive care unit outreach nurse and primary team doctors., Conclusions: Although nurses value the automated rapid response system activation as a safety net to minimise delays in accessing urgent critical care resources, it does not address the sociocultural barriers inherent in escalation of care. Although the automated system led nurses to be more cautious with vital signs monitoring, it does not encourage them to perform comprehensive patient assessments to detect early signs of deterioration., Relevance to Clinical Practice: Nurse education on assessing for clinical deterioration should focus on the use of broader patient assessment skills other than vital signs. Sociocultural barriers to escalation of care remain a key issue that needs to be addressed by hospital management., No Patient or Public Contribution: No patients, service users, care-givers or members of the public were involved in the study., (© 2023 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

Aim: To develop and internally validate risk prediction models for subsequent clinical deterioration, unplanned ICU admission and death among ward patients following medical emergency team (MET) review. Design: A retrospective cohort study of 1500 patients who remained on a general ward following MET review at an Australian quaternary hospital. Method: Logistic regression was used to model (1) subsequent MET review within 48 h, (2) unplanned ICU admission within 48 h and (3) hospital mortality. Models included demographic, clinical and illness severity variables. Model performance was evaluated using discrimination and calibration with optimism‐corrected bootstrapped estimates. Findings are reported using the TRIPOD guideline for multivariable prediction models for prognosis or diagnosis. There was no patient or public involvement in the development and conduct of this study. Results: Within 48 h of index MET review, 8.3% (n = 125) of patients had a subsequent MET review, 7.2% (n = 108) had an unplanned ICU admission and in‐hospital mortality was 16% (n = 240). From clinically preselected predictors, models retained age, sex, comorbidity, resuscitation limitation, acuity‐dependency profile, MET activation triggers and whether the patient was within 24 h of hospital admission, ICU discharge or surgery. Models for subsequent MET review, unplanned ICU admission, and death had adequate accuracy in development and bootstrapped validation samples. Conclusion: Patients requiring MET review demonstrate complex clinical characteristics and the majority remain on the ward after review for deterioration. A risk score could be used to identify patients at risk of poor outcomes after MET review and support general ward clinical decision‐making. Relevance to clinical practice: Our risk calculator estimates risk for patient outcomes following MET review using clinical data available at the bedside. Future validation and implementation could support evidence‐informed team communication and patient placement decisions. [ABSTRACT FROM AUTHOR]

Background and Objectives: Sepsis represents a global health challenge and requires advanced diagnostic and prognostic approaches due to its elevated rate of morbidity and fatality. Our study aimed to assess the value of a novel set of six biomarkers combined with severity scores in predicting 28 day mortality among patients presenting with sepsis in the Emergency Department (ED). Materials and Methods: This single-center, observational, prospective cohort included sixty-seven consecutive patients with septic shock and sepsis enrolled from November 2020 to December 2022, categorized into survival and non-survival groups based on outcomes. The following were assessed: procalcitonin (PCT), soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1), the soluble form of the urokinase plasminogen activator receptor (suPAR), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and azurocidin 1 (AZU1), alongside clinical scores such as the Quick Sequential Organ Failure Assessment (qSOFA), Systemic Inflammatory Response Syndrome (SIRS), the Sequential Organ Failure Assessment (SOFA), the Acute Physiology and Chronic Health Evaluation II (APACHE II), the Simplified Acute Physiology Score II and III (SAPS II/III), the National Early Warning Score (NEWS), Mortality in Emergency Department Sepsis (MEDS), the Charlson Comorbidity Index (CCI), and the Glasgow Coma Scale (GCS). The ability of each biomarker and clinical score and their combinations to predict 28 day mortality were evaluated. Results: The overall mortality was 49.25%. Mechanical ventilation was associated with a higher mortality rate. The levels of IL-6 were significantly higher in the non-survival group and had higher AUC values compared to the other biomarkers. The GCS, SOFA, APACHEII, and SAPS II/III showed superior predictive ability. Combining IL-6 with suPAR, AZU1, and clinical scores SOFA, APACHE II, and SAPS II enhanced prediction accuracy compared with individual biomarkers. Conclusion: In our study, IL-6 and SAPS II/III were the most accurate predictors of 28 day mortality for sepsis patients in the ED. [ABSTRACT FROM AUTHOR]

Nucleosome assembly proteins (NAPs) have been identified as histone chaperons. Testis‐Specific Protein, Y‐Encoded‐Like (TSPYL) is a newly arisen NAP family in mammals. TSPYL2 can be transcriptionally induced by DNA damage and TGFβ causing proliferation arrest. TSPYL1, another TSPYL family member, has been poorly characterized and is the only TSPYL family member known to be causal of a lethal recessive disease in humans. This study shows that TSPYL1 and TSPYL2 play an opposite role in TGFβ signaling. TSPYL1 partners with the transcription factor FOXA1 and histone methyltransferase EZH2, and at the same time represses TGFBR1 and epithelial‐mesenchymal transition (EMT). Depletion of TSPYL1 increases TGFBR1 expression, upregulates TGFβ signaling, and elevates the protein stability of TSPYL2. Intriguingly, TSPYL2 forms part of the SMAD2/3/4 signal transduction complex upon stimulation by TGFβ to execute the transcriptional responses. Depletion of TSPYL2 rescues the EMT phenotype of TSPYL1 knockdown in A549 lung carcinoma cells. The data demonstrates the prime role of TSPYL2 in causing the dramatic defects in TSPYL1 deficiency. An intricate counter‐balancing role of TSPYL1 and TSPYL2 in regulating TGFβ signaling is also unraveled. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to clarify the relationship between oral frailty and oral dysbiosis among hospitalized patients aged ≥ 50 years. Methods: A prospective observational study was conducted. Number of teeth, masticatory ability, articulatory oral motor skill, tongue pressure, swallowing pressure, and choking were used to assess oral frailty. Saliva samples were collected from the oral cavity for bacterial culture. Results: A total 103 in patients enrolled and 53.4% suffered from oral frailty. Oral frailty was found to have a 3.07‐fold correlation with the presence of Enterobacterales in the oral cavity (p = 0.037), especially in poor articulatory oral motor skill, which showed at greater risk of Enterobacterales isolated from the oral cavity by 5.58‐fold (p = 0.01). Conclusion: Half of hospitalized patients was found to have oral frailty that was related to more Enterobacterales in the oral cavity. This evidence suggests that the enhancement of articulatory oral motor skills may serve as a potential strategy for mitigating the presence of Enterobacterales within the oral cavity. [ABSTRACT FROM AUTHOR]

Mental state deterioration in patients poses significant challenges in healthcare, potentially resulting in adverse outcomes for patients and continued reliance on restrictive interventions. Implementing evidence-based approaches such as a rapid response system that prioritises early identification and intervention can effectively manage adverse outcomes. However, little is known regarding the effectiveness of these interventions. The objective of this synthesis was to test and refine initial programme theories by synthesising evidence to understand what works, for whom and under what circumstances. Based on the realist synthesis methodology, we searched EMBASE, CINAHL, MEDLINE, the Cochrane Library and grey literature for evidence to inform contexts, mechanisms and outcomes on the functioning of a rapid response model. We identified 28 relevant sources encompassing peer-reviewed journal articles and grey literature. This synthesis identified three important elements that contribute to the effectiveness of a rapid response system for managing mental state deterioration: care processes, therapeutic practices and organisational support. Essential elements include improving confidence and clinical skills through training, timely assessment and intervention, teamwork, communication and the creation of governance structures for monitoring and evaluation. To ensure the effectiveness, an organisation must adopt a comprehensive approach that incorporates organisational support, resource allocation, training, clear communication channels and commitment to continuous quality improvement. However, implementing interventions within a complex healthcare system requires thoughtful consideration of the organisational culture and governance structures. By taking a comprehensive and holistic approach to improvement initiatives, organisations can strive to achieve optimal outcomes in managing mental state deterioration and improving patient care., (© 2024 The Authors. International Journal of Mental Health Nursing published by John Wiley & Sons Australia, Ltd.)

Purpose: In patients with septic shock and elevated lactate, there is limited evidence evaluating supplementary vasopressor use beyond vasopressin (AVP) and norepinephrine (NE). The purpose of this study is to describe vasopressor utilization and clinical outcomes based on lactate level. Methods: We conducted a retrospective study of patients with septic shock requiring NE. Patients were divided into 2 groups: baseline lactate level of ≥4 mmol/L (lactate group) or <4 mmol/L (control group). The primary outcome was supplementary utilization of AVP, phenylephrine (PE), epinephrine, and dopamine, in addition to background NE therapy between the 2 patient groups. Results: A total of 100 patients in each group were included. Mean baseline lactate was 7.6 mmol/L and 2.3 mmol/L in the study and control groups, respectively (P <.01). Combination therapy with NE plus AVP (55% vs 26%; P <.01), NE plus PE (26% vs 3%; P <.01), and NE, AVP, plus PE (17% vs 0%; P <.01) was more common in the lactate group. On regression analysis, lactate group was a predictor of using AVP (OR 3.0; 95% CI 1.6-5.9), PE (OR 7.5; 95% CI 2.1-26.7), and AVP plus PE (OR 11.1; 95% CI 2.5-49.7). Conclusions: In this small retrospective study, multiple vasopressor use was high in patients with severely elevated lactate. The optimal vasopressor regimen in this patient population needs further investigation. [ABSTRACT FROM AUTHOR]

Background: Blood lactate is a potentially useful biomarker to predict the mortality and severity of sepsis. The purpose of this study is to systematically review the ability of lactate to predict hierarchical sepsis clinical outcomes and distinguish sepsis, severe sepsis and septic shock. Methods: We conducted an exhaustive search of the PubMed, Embase and Cochrane Library databases for studies published before 1 October 2022. Inclusion criteria mandated the presence of case–control, cohort studies and randomized controlled trials that established the association between before-treatment blood lactate levels and the mortality of individuals with sepsis, severe sepsis or septic shock. Data was analyzed using STATA Version 16.0. Results: A total of 127 studies, encompassing 107,445 patients, were ultimately incorporated into our analysis. Meta-analysis of blood lactate levels at varying thresholds revealed a statistically significant elevation in blood lactate levels predicting mortality (OR = 1.57, 95% CI 1.48–1.65, I2 = 92.8%, p < 0.00001). Blood lactate levels were significantly higher in non-survivors compared to survivors in sepsis patients (SMD = 0.77, 95% CI 0.74–0.79, I2 = 83.7%, p = 0.000). The prognostic utility of blood lactate in sepsis mortality was validated through hierarchical summary receiver operating characteristic curve (HSROC) analysis, yielding an area under the curve (AUC) of 0.72 (95% CI 0.68–0.76), accompanied by a summary sensitivity of 0.65 (95% CI 0.59–0.7) and a summary specificity of 0.7 (95% CI 0.64–0.75). Unfortunately, the network meta-analysis could not identify any significant differences in average blood lactate values' assessments among sepsis, severe sepsis and septic shock patients. Conclusions: This meta-analysis demonstrated that high-level blood lactate was associated with a higher risk of sepsis mortality. Lactate has a relatively accurate predictive ability for the mortality risk of sepsis. However, the network analysis found that the levels of blood lactate were not effective in distinguishing between patients with sepsis, severe sepsis and septic shock. [ABSTRACT FROM AUTHOR]

Aims: To identify and characterize the thematic foci, structure and evolution of nursing research on surveillance and patient safety. Design: Bibliometric analysis. Methods: Bibliometric methods were employed to analyse 1145 articles, using Bibliometrix and VOSviewer software. Data Source: The Scopus bibliographic database was searched on April 7, 2023. Results: A keyword co‐occurrence analysis found the most frequently occurring keywords to be: patient safety, nursing, nurses, adverse events, monitoring, critical care, quality improvement, vital signs, safety, alarm fatigue, education, nursing care, surveillance, clinical alarms, failure to rescue, evidence‐based practice, acute care, clinical deterioration, communication, intensive care. Network mapping, clustering and time‐tracking of the keywords revealed the focal themes, structure and evolution of the research field. Conclusion: By assessing critical areas of the nursing research field, this study extends and enriches the current discourse on surveillance and patient safety for nursing researchers and practitioners. Critical challenges still have to be met by nurses, however, including the failure to rescue deteriorating patients. Further knowledge and understanding of surveillance and patient safety must be successfully translated from research to practice. Implications for the Profession: This study highlights the gaps in nursing knowledge with regard to surveillance and patient safety and encourages nursing professionals to turn to evidence‐based surveillance practices. Impact: In addressing the problem of surveillance and its effect on patient safety, this study found that, in most clinical care settings, preventing failures to rescue and adverse patient outcomes still remains a challenge for the nursing profession. This study should have an impact on nursing academics' future research themes and on nursing professionals' future clinical practices. Reporting Method: Relevant EQUATOR guidelines have been adhered to by employing recognized bibliometric reporting methods. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Sepsis stands as the primary cause behind intensive care unit (ICU) admissions. The most critical parameters in sepsis management have been shown to be early recognition. Management delays have been associated with increased mortality and morbidity The aim of this study is to study the lactate/albumin (L/A) ratio as prognostic tool for risk stratification in septic patients admitted to ICU. MATERIALS AND METHODS: This prospective observational study was conducted with100 patients. Admitted in ICU with sepsis and septic shock were studied. Serum lactate/albumin ratio was calculated at the time of admission. Apache 2 and SOFA score was calculated at admission. All patients received initial treatment according standard protocol. All patients were followed up till discharge. An adverse outcome in terms of in hospital mortality, length of ICU stays and inotropic support was used in this study. RESULTS: Lactate/albumin ratio >1.5(AUC 0.89) correctly predicted in-hospital mortality among 27% patients with sensitivity and specificity of 90% and 78.6% respectively (p value =0.001). Lactate/albumin ratio <1.50 (AUC 0.73) correctly predicted length of ICU stays <72 hours among 17% patients with sensitivity and specificity of 85% and 58.8% respectively (p value =0.001). Lactate/albumin ratio >1.50 (AUC 0.91) correctly predicted requiring inotropic support among 36% patients with sensitivity and specificity of 83.7% and 89.5% respectively (p value =0.001). CONCLUSIONS: We concluded that lactate/albumin ratio was a stronger parameter than lactate, albumin, APACHE score and SOFA alone in predicting mortality, length of ICU stay and requiring noradrenaline inotropic support among sepsis patients in the ICU. [ABSTRACT FROM AUTHOR]

Aim: A medical emergency team (MET) stand‐down decision is the decision to end a MET response and hand responsibility for the patient back to ward staff for ongoing management. Little research has explored this decision. This study aimed to obtain expert consensus on the essential elements required to make optimal MET call stand‐down decisions and the communication required before MET departure. Design: A Delphi design was utilised. Methods: An expert panel of 10 members were recruited based on their expert knowledge and recent clinical MET responder experience in acute hospital settings. Participants were emailed a consent form and an electronic interactive PDF for each survey. Two rounds were conducted with no attrition between rounds. The CREDES guidance on conducting and reporting Delphi studies was used to report this study. Results: Consensus by an expert panel of 10 MET responders generated essential elements of MET stand‐down decisions. Essential elements comprised of two steps: (1) the stand‐down decision that was influenced by both the patient situation and the ward/organisational context; and (2) the communication required before actioning stand‐down. Communication after the decision required both verbal discussions and written documentation to hand over patient responsibility. Specific patient information, a management plan and an escalation plan were considered essential. Conclusion: The Delphi surveys reached consensus on the actions and communication required to stand down a MET call. Passing responsibility back to ward staff after a MET call requires both patient and ward safety assessments, and a clearly articulated patient plan for ward staff. Observation of MET call stand‐down decision‐making is required to validate the essential elements. Implication for the Profession and Patient/or Patient Care: In specifying the essential elements, this study offers clinical and MET staff a process to support the handing over of clinical responsibility from the MET to the ward staff, and clarification of management plans in order to reduce repeat MET calls and improve patient outcomes. Impact: Minimal research has been focussed on the decision to hand responsibility back to ward staff so the MET may leave the ward with safety plan in place. This study provided expert consensus to optimise MET stand‐down decision‐making and the ultimate decision to end a MET call. Communication of agreed patient treatment and escalation plans is recommended before leaving the ward. This study can be used as a checklist for MET responder staff making these decisions and ward staff responsible for post‐MET call care. The aim being to reduce the likelihood of potentially preventable repeat deterioration in the MET patient population. Reporting Method: The CREDES guidance on conducting and reporting Delphi studies. Patient or Public Contribution: None. [ABSTRACT FROM AUTHOR]

The beneficial effects of a rapid response system (RRS) on clinical outcomes in patients admitted to a ward have been established. However, the relationship between RRS implementation and clinical outcomes in patients in the intensive care unit (ICU) has not yet been established. Therefore, we aimed to investigate whether the RRS affects clinical outcomes in critically ill patients admitted to the ICU. As a nationwide, population-based cohort study, all adult patients who were admitted to the ICU from 1 January 2019 to 31 December 2021 in South Korea were included. Patients in hospitals with an RRS formed the RRS group; those in hospitals lacking an RRS constituted the non-RRS group. In total, 900,606 patients admitted to the ICU were included in the final analysis. Among them, 365,305 (40.6%) were assigned to the RRS group, and 535,301 (59.4%) were assigned to the non-RRS group. After propensity score (PS) matching, a total of 454,748 patients (227,374 in each group) were included in the final analysis. In the PS-matched cohort, the RRS group showed 8% (odds ratio [OR]: 0.92, 95% confidence interval [CI]: 0.91, 0.94; P < 0.001) and 11% (hazard ratio: 0.89, 95% CI: 0.88, 0.90; P < 0.001) lower in-hospital mortality rates and 1-year all-cause mortality rates than the non-RRS group, respectively. In addition, ICU readmission rates and the occurrence rate for adverse events during hospitalization in the RRS group were 3% (OR: 0.97, 95% CI: 0.95, 0.98; P < 0.001) and 21% (OR: 0.79, 95% CI: 0.78, 0.80; P < 0.001) lower than those in the non-RRS group, respectively. RRS deployment was linked to lower in-hospital and 1-year all-cause mortality rates, ICU readmission rates, and the occurrence of adverse events during hospitalization among ICU patients. The findings indicate that using the RRS could assist not only patients in the ward but also critically ill patients in the ICU., (© 2024. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

This study surveys the differences of relatively healthy proponents of end-of-life choices and people with irremediable health conditions having already made the decision to hasten their deaths on what each group considers important in influencing a desire to hasten death. Psychosocial factors were more important than physical ones for both groups; but those contemplating what might influence them to hasten their deaths in the future thought pain and feeling ill would be much bigger factors than they turned out to be for those deciding to do so. Those having decided to hasten their deaths cited the lack of any further viable medical treatments and having to live in a nursing home as bigger factors. Identifying these psychosocial factors influencing a desire for a hastened death suggests that caregivers and medical providers may want to review what compassionate understanding and support looks like for people wanting to hasten their death. [ABSTRACT FROM AUTHOR]

Rapid Response Systems (RRS) improve patient outcomes at large medical centers. Little is known about how RRS are used in other medical settings. The purpose of this exploratory study was to describe RRS events at a long-term acute care hospital (LTACH). We conducted a retrospective review of 71 RRS event records at an urban 50-bed Midwestern LTACH. Measures included demographic data, triggering mechanisms, contextual factors, mechanism factors, and clinical outcomes. Of patients who experienced a RRS event, median age was 71 (62, 80) years; 52.1% were female; most (n = 49, 69%) were "full code." Most (n = 41, 58%) events occurred during the daytime. The most common trigger was "mental status changes/unresponsiveness." Registered nurses were the most frequent activator (n = 19, 26.8%) and responders (n = 63, 60.6%). Median duration of RRS events was 14 (6, 25) minutes. Most patients stabilized and their condition improved (n = 54, 76.1%). RRS can be expanded and modified to the LTACH population. [ABSTRACT FROM AUTHOR]

Serum lactate is a potentially valuable biomarker for risk assessment for patients with sepsis, as hyperlactatemia is associated with elevated short-term mortality risks. However, the associations between hyperlactatemia and long-term clinical outcomes in sepsis survivors remain unknown. The objective of this study was to investigate whether hyperlactatemia at the time of hospitalisation for sepsis was associated with worse long-term clinical outcomes in sepsis survivors. In total, of 4983 sepsis survivors aged ≥ 20 years were enrolled in this study between January 1, 2012, and December 31, 2018. They were divided into low (≤18 mg/dL; n = 2698) and high (>18 mg/dL; n = 2285) lactate groups. The high lactate group was then matched 1:1 by propensity-score method to the low lactate group. The outcomes of interest were all-cause mortality, major adverse cardiac events (MACEs), ischaemic stroke, myocardial infarction, hospitalisation for heart failure, and end-stage renal disease. After propensity score matching, the high lactate group had greater risks of all-cause mortality (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.41–1.67), MACEs (HR 1.53, 95% CI 1.29–1.81), ischaemic stroke (HR 1.47, 95% CI 1.19–1.81), myocardial infarction (HR 1.52, 95% CI 1.17–1.99), and end-stage renal disease (HR 1.42, 95% CI 1.16–1.72). Subgroup analyses stratified by baseline renal function revealed almost similarity across groups. We found that hyperlactatemia is associated with long-term risks of mortality and MACEs in sepsis survivors. Physicians may consider more aggressive and prompter management of sepsis in patients who present with hyperlactatemia to improve long-term prognoses. [ABSTRACT FROM AUTHOR]

Urinary tract infection (UTI) is a common condition that predominantly affects elderly people, who are particularly susceptible to developing sepsis. Previous studies have indicated a detrimental effect of sepsis on short-term outcomes in elderly patients with UTI, but there is a lack of data about the middle-term prognosis. The aim of this study was to investigate the influence of sepsis on the middle-term prognosis of patients aged 65 years or older with complicated community-acquired UTIs. A prospective observational study of patients admitted to a hospital with UTI. We conducted a comparison of epidemiological and clinical variables between septic and nonseptic patients with UTI, as well as their 6-month case-fatality rate. A total of 412 cases were included, 47.8% of them with sepsis. Septic patients were older (83 vs. 80 years, p < 0.001), but did not have more comorbidities. The short-term case-fatality rate was higher in septic patients and this difference persisted at 6 months (34% vs. 18.6%, p = 0.003). Furthermore, age older than 75 years, Barthel index <40 and healthcare-associated UTI were also associated with the middle-term case-fatality rate. In conclusion, the detrimental impact of sepsis is maintained on the middle-term prognosis of elderly patients with UTI. Age, functional status and healthcare-associated UTIs also play significant roles in shaping patient outcomes. [ABSTRACT FROM AUTHOR]

Intraoperative fluid therapy is regularly used in patients undergoing cardiac surgery procedures with cardiopulmonary bypass (CPB). Although fluid administration has several advantages, it unavoidably leads to hemodilution. The hemodilution may further influence the interpretation of concentration-based laboratory parameters like hemoglobin (Hgb), platelet count (PLT) or prothrombin time (PT). These all parameters are commonly used to guide blood product substitution. To assess the impact of dilution on these values, we performed a prospective observational study in 174 patients undergoing elective cardiac surgery. We calculated the total blood volume according to Nadler's formula, and fluid therapy was correlated with a newly developed dilution coefficient formula at the end of CPB. Intravenously applied fluids were measured from the beginning of the anesthesia (baseline, T0) and 15 min after the end of protamine infusion (end of CPB, T1). The amount of the administered volume (crystalloids or colloids) was calculated according to the percentage of the intravascular fluid effect, and intraoperative diuresis was further subtracted. The median blood volume increased by 148% in all patients at T1 compared to the calculated total blood volume at T0. This led to a dilution-dependent decrease of 38% in all three parameters (Hgb 24%, corrCoeff = 0.53; PLT 41%, corrCoeff = 0.68; PT 44%, corrCoeff = 0.54). The dilution-correlated decrease was significant for all parameters (p < 0.001), and the effect was independent from the duration of CPB. We conclude that the presented calculation-based approach could provide important information regarding actual laboratory parameters and may help in the guidance of the blood product substitution and potential transfusion thresholds. Further research on the impact of dilution and related decision-making for blood product substitution, including its impact on morbidity and mortality, is warranted. [ABSTRACT FROM AUTHOR]

Background: Outcomes associated with rapid response teams (RRTs) are inconsistent. This may be due to underlying facilitators and barriers to RRT activation that are affected by team leaders and health systems., Aims: The aim of this study was to synthesize the published research about facilitators and barriers to nurse-led RRT activation in the United States (U.S.)., Methods: A systematic review was conducted. Four databases were searched from January 2000 to June 2023 for peer-reviewed quantitative, qualitative, and mixed methods studies reporting facilitators and barriers to RRT activation. Studies conducted outside the U.S. or with physician-led teams were excluded., Results: Twenty-five studies met criteria representing 240,140 participants that included clinicians and hospitalized adults. Three domains of facilitators and barriers to RRT activation were identified: (1) hospital infrastructure, (2) clinician culture, and (3) nurses' beliefs, attributes, and knowledge. Categories were identified within each domain. The categories of perceived benefits and positive beliefs about RRTs, knowing when to activate the RRT, and hospital-wide policies and practices most facilitated activation, whereas the categories of negative perceptions and concerns about RRTs and uncertainties surrounding RRT activation were the dominant barriers., Linking Evidence to Action: Facilitators and barriers to RRT activation were interrelated. Some facilitators like hospital leader and physician support of RRTs became barriers when absent. Intradisciplinary communication and collaboration between nurses can positively and negatively impact RRT activation. The expertise of RRT nurses should be further studied., (© 2023 Sigma Theta Tau International.)

Electronic health records (EHRs) are used in hospitals to store diagnoses, clinician notes, examinations, lab results, and interventions for each patient. Grouping patients into distinct subsets, for example, via clustering, may enable the discovery of unknown disease patterns or comorbidities, which could eventually lead to better treatment through personalized medicine. Patient data derived from EHRs is heterogeneous and temporally irregular. Therefore, traditional machine learning methods like PCA are ill-suited for analysis of EHR-derived patient data. We propose to address these issues with a new methodology based on training a gated recurrent unit (GRU) autoencoder directly on health record data. Our method learns a low-dimensional feature space by training on patient data time series, where the time of each data point is expressed explicitly. We use positional encodings for time, allowing our model to better handle the temporal irregularity of the data. We apply our method to data from the Medical Information Mart for Intensive Care (MIMIC-III). Using our data-derived feature space, we can cluster patients into groups representing major classes of disease patterns. Additionally, we show that our feature space exhibits a rich substructure at multiple scales. [ABSTRACT FROM AUTHOR]

This review critiques the benefits and drawbacks of the United Kingdom's National Early Warning Score (NEWS). Potential developments for the future are considered, as well as the role for NEWS in an emergency department (ED). The ability of NEWS to predict death within 24 h has been well validated in multiple clinical settings. It provides a common language for the assessment of clinical severity and can be used to trigger clinical interventions. However, it should not be used as the only metric for risk stratification as its ability to predict mortality beyond 24 h is not reliable and greatly influenced by other factors. The main drawbacks of NEWS are that measuring it requires trained professionals, it is time consuming and prone to calculation error. NEWS is recommended for use in acute UK hospitals, where it is linked to an escalation policy that reflects postgraduate experience; patients with lower NEWS are first assessed by a junior clinician and those with higher scores by more senior staff. This policy was based on expert opinion that did not consider workload implications. Nevertheless, its implementation has been shown to improve the efficient recording of vital signs. How and who should respond to different NEWS levels is uncertain and may vary according to the clinical setting and resources available. In the ED, simple triage scores which are quicker and easier to use may be more appropriate determinants of acuity. However, any alternative to NEWS should be easier and cheaper to use and provide evidence of outcome improvement. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to explore the association of serum lactate with clinical outcomes in elderly patients with sepsis based on data from the MIMIC-IV database. Methods: All elderly patients with sepsis (age ≥ 65 years) were included. Different models were constructed for exploring the relationships between lactate and 28-day mortality. A two-segment linear regression model was performed to verify the threshold effects of lactate on clinical outcomes and smooth curve fitting was performed. Results: A total of 4199 elderly patients with sepsis were included. The 28-day mortality was 32.22% (n = 1395). After adjustment for all potential cofounders, for each 1 mmol/l increment in lactate, the odds ratio (OR) of 28-day mortality was 1.23 (95% CI 1.18–1.28, P < 0.0001). Smooth fitting curves indicated a non-linear positive relationship between lactate and 28-day mortality. The turning point of lactate level was 5.7 mmol/l: at ≤ 5.7 mmol/l, with each 1 mmol/l increment in lactate, the risk of 28-day mortality increased significantly (OR 1.32, 95% CI 1.25–1.38, P < 0.0001); the significantly positive relationship was still present at lactate > 5.7 mmol/l (OR 1.10, 95% CI 1.04–1.18, P = 0.0019). The area under the ROC curve (AUC) of lactate was 0.618 (95% CI 0.599–0.635) and the cutoff value of lactate was 2.4 mmol/l with a sensitivity of 0.483 and a specificity of 0.687. Conclusion: In elderly patients with sepsis, a non-linear positive relationship was discovered between serum lactate and 28-day mortality. Physicians should be alert to lactate assessment at admission and pay more attention to those patients with higher levels of lactate. [ABSTRACT FROM AUTHOR]

Introduction: The Plethysmographic Variability Index can be measured by both finger and forehead probes. Vasoconstriction may jeopardize the reliability of finger PVI measurements in pediatric patients undergoing surgery. However, forehead vasculature exhibits more marked resistance to alterations in the vasomotor tonus. Objective: Our aim was to compare the Plethysmographic Variability Index measured via finger or forehead probes in mechanically ventilated pediatric surgery patients in terms of their ability to predict fluid responsiveness as well as to determine the best cut‐off values for these two measurements. Materials and Methods: A total of 50 pediatric patients undergoing minor elective surgery were included after provision of parental consent and ethics committee approval. Perfusion index measured at the finger or forehead and Plethysmographic Variability Index monitoring comprised the primary assessments. Hemodynamic parameters monitored included perfusion index, Plethysmographic Variability Index, and cardiac output. A ≥ 15% increase in cardiac output following passive leg raise maneuver was considered to show fluid responsiveness. Two groups were defined based on fluid responsiveness: Group R (responsive) and Group NR (non‐responsive). Student's t‐test, Mann–Whitney U test, DeLong test, and ROC were used for statistical analysis. Results: The area under curve for finger and forehead Plethysmographic Variability Index prior to passive leg raise maneuver were 0.699 (p =.011) and 0.847 (p <.001), respectively. The sensitivity for finger and forehead measurements at a cut‐off value of ≤14% was 92.9% and 96.4%, and 45.4% and 72.7%, respectively. Conclusion: Although forehead and finger Plethysmographic Variability Index monitoring were similarly sensitive in predicting fluid responsiveness in pediatric surgical patients, the former method provided higher specificity. The best cut‐off value for PVI measurements with forehead and finger probes was found to be 14%. [ABSTRACT FROM AUTHOR]

Objective: Early identifying sepsis patients who had higher risk of poor prognosis was extremely important. The aim of this study was to develop an artificial neural networks (ANN) model for early predicting clinical outcomes in sepsis. Methods: This study was a retrospective design. Sepsis patients from the Medical Information Mart for Intensive Care-III (MIMIC-III) database were enrolled. A predictive model for predicting 30-day morality in sepsis was performed based on the ANN approach. Results: A total of 2874 patients with sepsis were included and 30-day mortality was 29.8%. The study population was categorized into the training set (n = 1698) and validation set (n = 1176) based on the ratio of 6:4. 11 variables which showed significant differences between survivor group and nonsurvivor group in training set were selected for constructing the ANN model. In training set, the predictive performance based on the area under the receiver-operating characteristic curve (AUC) were 0.873 for ANN model, 0.720 for logistic regression, 0.629 for APACHEII score and 0.619 for SOFA score. In validation set, the AUCs of ANN, logistic regression, APAHCEII score, and SOFA score were 0.811, 0.752, 0.607, and 0.628, respectively. Conclusion: An ANN model for predicting 30-day mortality in sepsis was performed. Our predictive model can be beneficial for early detection of patients with higher risk of poor prognosis. [ABSTRACT FROM AUTHOR]

Aim and Objective: To explore Rapid Response Team nurses' perceptions of what it means being a Rapid Response Team nurse including their perceptions of the collaborative and organisational aspects of the rapid response team (RRT). Background: For more than 20 years, RRT nurses have been on the frontline of critical situations in acute care hospitals. However, a few studies report nurses' perceptions of their role as RRT nurses, including collaboration with general ward nurses and physicians. This knowledge is important to guide development and adjustment of the RRT to benefit both patients' safety and team members' job satisfaction. Design: Qualitative focus group interviews. Methods: A qualitative approach was applied. Throughout 2018 and across three regions and three acute care settings in Denmark, eight focus group interviews were conducted in which 27 RRT nurses participated. Transcribed interviews were analysed using inductive content analysis. Reporting of this study followed the COREQ checklist. Results: One overarching theme 'Balancing responsibilities, rewards, and challenges' was derived, comprising six categories: 'Becoming, developing and fulfilling the RRT nurse role', 'Helping patients as the core function of RRT', 'The RRT‐call at its best', 'The obvious and the subtle RRT tasks', 'Carrying the burden of the RRT', and 'Organisational benefits and barriers for an optimal RRT'. Conclusion: Being a RRT nurse is a complex task. Nurses experience professional satisfaction and find it meaningful helping deteriorating patients. The inadequate resources available to train general ward staff how to manage basic clinical tasks are an added stress to nurses. Relevance to clinical practice: Organisational managers need a better understanding of the necessary staffing requirements to attend patients' needs, train staff and handle the increasing acuity of ward patients. Failure to do so will be detrimental to patient outcomes and compromise RRT nurses' job satisfaction. [ABSTRACT FROM AUTHOR]

Transforming growth factor–β (TGF-β) signaling regulates various aspects of cell growth and differentiation and is often dysregulated in human cancers. We combined genetic engineering of a human organotypic three-dimensional (3D) skin model with global quantitative proteomics and phosphoproteomics to dissect the importance of essential components of the TGF-β signaling pathway, including the ligands TGF-β1, TGF-β2, and TGF-β3, the receptor TGF-βRII, and the intracellular effector SMAD4. Consistent with the antiproliferative effects of TGF-β signaling, the loss of TGF-β1 or SMAD4 promoted cell cycling and delayed epidermal differentiation. The loss of TGF-βRII, which abrogates both SMAD4-dependent and SMAD4-independent downstream signaling, more strongly affected cell proliferation and differentiation than did loss of SMAD4, and it induced invasive growth. TGF-βRII knockout reduced cell-matrix interactions, and the production of matrix proteins increased the production of cancer-associated cell-cell adhesion proteins and proinflammatory mediators and increased mitogen-activated protein kinase (MAPK) signaling. Inhibiting the activation of the ERK and p38 MAPK pathways blocked the development of the invasive phenotype upon the loss of TGF-βRII. This study provides a framework for exploring TGF-β signaling pathways in human epithelial tissue homeostasis and transformation using genetic engineering, 3D tissue models, and high-throughput quantitative proteomics and phosphoproteomics. Modeling TGF-β signaling in human skin: Studies in mice and human tumors have identified multiple roles for TGF-β signaling in normal skin biology and in the development and progression of skin cancers. To investigate the requirements for TGF-β signaling in human epidermal development and homeostasis, Ye et al. performed phenotypic and quantitative proteomic and phosphoproteomic analyses of an in vitro model of stratified human epidermis with knockout of individual TGF-β signaling components. Whereas SMAD4-dependent signaling was important for limiting epidermal proliferation and promoting differentiation and cell adhesion, SMAD4-independent signaling was important for preventing invasive growth by suppressing signaling through MAPK pathways. The proteomic and phosphoproteomic data will enable future studies investigating TGF-β signaling in normal and pathological contexts, and the human epidermis model could be exploited for future drug discovery efforts. [ABSTRACT FROM AUTHOR]

Introduction: Hyperlactatemia is a regular condition in the intensive care unit, which is often associated with adverse outcomes. Control of the triggering condition is the most effective treatment of hyperlactatemia, but since this is mostly not readily possible, extracorporeal renal replacement therapy (RRT) is often tried as a last resort. The present study aims to evaluate the factors that may contribute to the decision whether to start RRT or not and the potential impact of the start of RRT on the outcome in patients with severe lactic acidosis (SLA) (lactate ≥5 mmol/L). Materials and Methods: We conducted a retrospective single-center cohort analysis over a 3-year period including all patients with a lactate level ≥5 mmol/L. Patients were considered as treated with RRT because of SLA if RRT was started within 24 h after reaching a lactate level ≥5 mmol/L. Results: Overall, 90-day mortality in patients with SLA was 34.5%. Of the 1,203 patients who matched inclusion/exclusion criteria, 11% (n = 133) were dialyzed within 24 h. The propensity to receive RRT was related to the lactate level and to the SOFA renal and cardio score. The most frequently used modality was continuous RRT. Patients who were started on RRT versus those who did not have 2.3 higher odds of mortality, even after adjustment for the propensity to start RRT. Conclusions: Our analysis confirms the high mortality rate of patients with SLA. It adds that odds for mortality is even higher in patients who were started on RRT versus not. We suggest keeping an open mind to the factors that may influence the decision to start dialysis and bear in mind that without being a bridge to correction of the underlying condition, dialysis is unlikely to affect the outcome. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine what, how, and under what circumstances individual-focused interventions improve well-being and decrease burnout for critical care healthcare professionals. Method: This realist approach, expert opinion interview, was guided by the Realist And Meta-narrative Evidence Synthesis: Evolving Standards II (RAMESES II) guidelines. Semi-structured interviews with critical care experts were conducted to ascertain current and nuanced information on a set of predefined individual interventions summarized from a previous umbrella review. The data were appraised, and relationships between context, mechanisms, and outcomes were extracted, which created theory prepositions that refined the initial program theory. Results: A total of 21 critical care experts were individually interviewed. By understanding the complex interplay between organizational and personal factors that influenced intervention uptake, it was possible to decipher the most likely implementable intervention for critical care healthcare professionals. The expert recommendation suggested that interventions should be evidence-based, accessible, inclusive, and collaborative, and promote knowledge and skill development. Unique mechanisms were also required to achieve the positive effects of the intervention due to the presence of contextual factors within critical care settings. Mechanisms identified in this study included the facilitation of self-awareness, self-regulation, autonomy, collaboration, acceptance, and inclusion (to enable a larger reach to different social groups). Conclusion: This validation of a theoretical understanding of intervention that addressed well-being and burnout in critical care healthcare professionals by expert opinion demonstrated essential mechanisms and contextual factors to consider when designing and implementing interventions. Future research would benefit by piloting individual interventions and integrating these new theoretical findings to understand better their effectiveness for future translation into the “real-world” setting. [ABSTRACT FROM AUTHOR]

The therapeutic challenges pertaining to leishmaniasis due to reported chemoresistance and toxicity necessitate the need to explore novel pathways to identify plausible inhibitory molecules. Leishmania donovani 24-sterol methyltransferase (Ld SMT) is vital for the synthesis of ergosterols, the main constituents of Leishmania cellular membranes. So far, mammals have not been shown to possess SMT or ergosterols, making the pathway a prime candidate for drug discovery. The structural model of Ld SMT was elucidated using homology modeling to identify potential novel 24-SMT inhibitors via virtual screening, scaffold hopping, and de-novo fragment-based design. Altogether, six potential novel inhibitors were identified with binding energies ranging from −7.0 to −8.4 kcal/mol with e-LEA3D using 22,26-azasterol and S1 – S4 obtained from scaffold hopping via the ChEMBL, DrugBank, PubChem, ChemSpider, and ZINC15 databases. These ligands showed comparable binding energy to 22,26-azasterol (−7.6 kcal/mol), the main inhibitor of Ld SMT. Moreover, all the compounds had plausible ligand efficiency-dependent lipophilicity (LELP) scores above 3. The binding mechanism identified Tyr92 to be critical for binding, and this was corroborated via molecular dynamics simulations and molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) calculations. The ligand A1 was predicted to possess antileishmanial properties with a probability of activity (Pa) of 0.362 and a probability of inactivity (Pi) of 0.066, while A5 and A6 possessed dermatological properties with Pa values of 0.205 and 0.249 and Pi values of 0.162 and 0.120, respectively. Structural similarity search via DrugBank identified vabicaserin, daledalin, zanapezil, imipramine, and cefradine with antileishmanial properties suggesting that the de-novo compounds could be explored as potential antileishmanial agents. [ABSTRACT FROM AUTHOR]

Delayed admission of patients to the intensive care unit (ICU) is increasing worldwide and can be followed by adverse outcomes when critical care treatment is not provided timely. This systematic review and meta-analysis appraised and synthesized the published literature about the association between delayed ICU admission and mortality of adult patients. Articles published from inception up to August 2021 in English-language, peer-reviewed journals indexed in CINAHL, PubMed, Scopus, Cochrane Library, and Web of Science were searched by using key terms. Delayed ICU admission constituted the intervention, while mortality for any predefined time period was the outcome. Risk for bias was evaluated with the Newcastle-Ottawa Scale and additional criteria. Study findings were synthesized qualitatively, while the odds ratios (ORs) for mortality with 95% confidence intervals (CIs) were combined quantitatively. Thirty-four observational studies met inclusion criteria. Risk for bias was low in most studies. Unadjusted mortality was reported in 33 studies and was significantly higher in the delayed ICU admission group in 23 studies. Adjusted mortality was reported in 18 studies, and delayed ICU admission was independently associated with significantly higher mortality in 13 studies. Overall, pooled OR for mortality in case of delayed ICU admission was 1.61 (95% CI 1.44-1.81). Interstudy heterogeneity was high ( I 2 = 66.96 %). According to subgroup analysis, OR for mortality was remarkably higher in postoperative patients (OR, 2.44, 95% CI 1.49-4.01). These findings indicate that delayed ICU admission is significantly associated with mortality of critically ill adults and highlight the importance of providing timely critical care in non-ICU settings. [ABSTRACT FROM AUTHOR]

The tremendous public health problem created by substance use disorders (SUDs) presents a major opportunity for mouse genetics. Inbred mouse strains exhibit substantial and heritable differences in their responses to drugs of abuse (DOA) and in many of the behaviors associated with susceptibility to SUD. Therefore, genetic discoveries emerging from analysis of murine genetic models can provide critically needed insight into the neurobiological effects of DOA, and they can reveal how genetic factors affect susceptibility drug addiction. There are already indications, emerging from our prior analyses of murine genetic models of responses related to SUDs that mouse genetic models of SUD can provide actionable information, which can lead to new approaches for alleviating SUDs. Lastly, we consider the features of murine genetic models that enable causative genetic factors to be successfully identified; and the methodologies that facilitate genetic discovery. [ABSTRACT FROM AUTHOR]

Estrogen-related receptor (ERR) is a member of the nuclear receptor (NR) superfamily and has three subtypes α, β, and γ. Despite their strong homology with estrogen receptor (ER) α, ERRs cannot accommodate endogenous hormones. However, they are able to regulate gene expression without ligand binding. ERRα and ERRγ orchestrate the expression of genes involved in bioenergetic pathways, while ERRβ controls placental development and stem cell maintenance. Evidence from recent studies, including clinical research, has also demonstrated close associations of ERRs with the pathophysiology of hormone-related cancers and metabolic disorders including type 2 diabetes mellitus. This review summarizes the basic knowledge and recent advances in ERRs and their associated proteins, focusing on the subcellular dynamics involved in transcriptional regulation. Fluorescent protein labeling enabled monitoring of ERRs in living cells and revealed previously unrecognized characteristics. Using this technique, we demonstrated a role of ERRβ in controlling estrogen signaling by regulating the subnuclear dynamics of ligand-activated ERα. Visualization of ERRs and related proteins and subsequent analyses also revealed a function of ERRγ in promoting liver lactate metabolism in association with LRPGC1, a recently identified lactic acid-responsive protein. These findings suggest that ERRs activate unique transregulation mechanisms in response to extracellular stimuli such as hormones and metabolic signals, implying an adaptive system behind the cellular homeostatic regulation by orphan NRs. Control of subcellular ERR dynamics will contribute toward the development of therapeutic approaches to treat various diseases including hormone-related cancers and metabolic disorders associated with abnormal ERR signaling pathways. [ABSTRACT FROM AUTHOR]

Objective: Our primary aim was to assess selected metabolic dysfunction parameters, both independently and as a complement to the SOFA score, as predictors of short-term mortality in patients with infection admitted to the intensive care unit (ICU).Methods: We retrospectively enrolled all consecutive adult patients admitted to the eight ICUs of Lille University Hospital, between January 2015 and September 2016, with suspected or confirmed infection. We selected seven routinely measured biological and clinical parameters of metabolic dysfunction (maximal arterial lactatemia, minimal and maximal temperature, minimal and maximal glycaemia, cholesterolemia, and triglyceridemia), in addition to age and the Charlson's comorbidity score. All parameters and SOFA scores were recorded within 24 h of admission.Results: We included 956 patients with infection, among which 295 (30.9%) died within 90 days. Among the seven metabolic parameters investigated, only maximal lactatemia was associated with higher risk of 90-day hospital mortality in SOFA-adjusted analyses (SOFA-adjusted OR, 1.17; 95%CI, 1.10 to 1.25; p < 0.001). Age and the Charlson's comorbidity score were also statistically associated with a poor prognosis in SOFA-adjusted analyses. We were thus able to develop a metabolic failure, age, and comorbidity assessment (MACA) score based on scales of lactatemia, age, and the Charlson's score, intended for use in combination with the SOFA score.Conclusions: The maximal lactatemia level within 24 h of ICU admission is the best predictor of short-term mortality among seven measures of metabolic dysfunction. Our combined "SOFA + MACA" score could facilitate early detection of patients likely to develop severe infections. Its accuracy requires further evaluation. [ABSTRACT FROM AUTHOR]

The evaluation and management of fluid balance are key challenges when caring for critically ill patients requiring renal replacement therapy. The aim of this study was to assess the ability of clinical judgment and other variables to predict the occurrence of hypotension during intermittent hemodialysis (IHD) in critically ill patients. This was a prospective, observational, single-center study involving critically ill patients undergoing IHD. The clinical judgment of hypervolemia was determined by the managing nephrologists and critical care physicians in charge of the patients on the basis of the clinical data used to calculate the ultrafiltration volume and rate for each dialysis treatment. Seventy-nine (31.9%) patients presented with hypotension during IHD. Patients were perceived as being hypervolemic in 109 (43.9%) of the cases by nephrologists and in 107 (43.1%) by intensivists. The agreement between nephrologists and intensivists was weak (kappa = 0.561). Receiver operating characteristic curve analysis yielded an AUC of 0.81 (95% CI 0.75 to 0.84; P < 0.0001), and a cutoff value of 70 mm for the vascular pedicle width (VPW) had the highest accuracy for the prediction of the absence of hypotension. The clinical judgment of hypervolemia did not predict hypotension during IHD. The high predictive ability of the VPW may assist clinicians with critical thinking. [ABSTRACT FROM AUTHOR]