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Extra-intestinal pathogenic Escherichia coli (ExPEC) belong to a critical priority group of antibiotic resistant pathogens. ExPEC establish gut reservoirs that seed infection of the urinary tract and bloodstream, but the mechanisms of gut colonisation remain to be properly understood. Ucl fimbriae are attachment organelles that facilitate ExPEC adherence. Here, we investigated cellular receptors for Ucl fimbriae and Ucl expression to define molecular mechanisms of Ucl-mediated ExPEC colonisation of the gut. We demonstrate differential expression of Ucl fimbriae in ExPEC sequence types associated with disseminated infection. Genome editing of strains from two common sequence types, F11 (ST127) and UTI89 (ST95), identified a single nucleotide polymorphism in the ucl promoter that changes fimbriae expression via activation by the global stress-response regulator OxyR, leading to altered gut colonisation. Structure-function analysis of the Ucl fimbriae tip-adhesin (UclD) identified high-affinity glycan receptor targets, with highest affinity for sialyllacto-N-fucopentose VI, a structure likely to be expressed on the gut epithelium. Comparison of the UclD adhesin to the homologous UcaD tip-adhesin from Proteus mirabilis revealed that although they possess a similar tertiary structure, apart from lacto-N-fucopentose VI that bound to both adhesins at low-micromolar affinity, they recognize different fucose- and glucose-containing oligosaccharides. Competitive surface plasmon resonance analysis together with co-structural investigation of UcaD in complex with monosaccharides revealed a broad-specificity glycan binding pocket shared between UcaD and UclD that could accommodate these interactions. Overall, our study describes a mechanism of adaptation that augments establishment of an ExPEC gut reservoir to seed disseminated infections, providing a pathway for the development of targeted anti-adhesion therapeutics.

Both inflow and the partial volume effect (PVE) are sources of error when measuring the arterial input function (AIF) in dynamic contrast-enhanced (DCE) MRI. This is relevant, as errors in the AIF can propagate into pharmacokinetic parameter estimations from the DCE data. A method was introduced for flow correction by estimating and compensating the number of the perceived pulse of spins during inflow. We hypothesized that the PVE has an impact on concentration-time curves similar to inflow. Therefore, we aimed to study the efficiency of this method to compensate for both effects simultaneously. We first simulated an AIF with different levels of inflow and PVE contamination. The peak, full width at half-maximum (FWHM), and area under curve (AUC) of the reconstructed AIFs were compared with the true (simulated) AIF. In clinical data, the PVE was included in AIFs artificially by averaging the signal in voxels surrounding a manually selected point in an artery. Subsequently, the artificial partial volume AIFs were corrected and compared with the AIF from the selected point. Additionally, corrected AIFs from the internal carotid artery (ICA), the middle cerebral artery (MCA), and the venous output function (VOF) estimated from the superior sagittal sinus (SSS) were compared. As such, we aimed to investigate the effectiveness of the correction method with different levels of inflow and PVE in clinical data. The simulation data demonstrated that the corrected AIFs had only marginal bias in peak value, FWHM, and AUC. Also, the algorithm yielded highly correlated reconstructed curves over increasingly larger neighbourhoods surrounding selected arterial points in clinical data. Furthermore, AIFs measured from the ICA and MCA produced similar peak height and FWHM, whereas a significantly larger peak and lower FWHM was found compared with the VOF. Our findings indicate that the proposed method has high potential to compensate for PVE and inflow simultaneously. The corrected AIFs could thereby provide a stable input source for DCE analysis., (© 2024 The Author(s). NMR in Biomedicine published by John Wiley & Sons Ltd.)

Introduction: Heterozygous pathogenic variants in NTRK2 (HGNC: 8032) have been associated with global developmental delay. However, only scattered cases have been described in small or general studies. The aim of our work was to consolidate our understanding of NTRK2-related disorders and to delineate the clinical presentation METHODS: We report extended cohort of 44 affected individuals, of whom 19 are from the literature and 25 were previously unreported., Results: Our analysis led to splitting the cohort into two entities., Discussion: One group had variants in the cholesterol binding motif of the transmembrane domain, with most of these being the recurrent variant c.1301A>G p.(Tyr434Cys). These variants probably lead to upregulation of TRKB activity and to a severe phenotype of developmental delay/intellectual disability, muscular hypotonia, therapy-refractory epilepsy, visual impairment and blindness, and feeding difficulties. The second group had truncating variants or variants that presumably disturb the 3D structure of the protein leading to loss of function. These individuals had a remarkably milder phenotype of developmental delay, obesity and hyperphagia., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Although financial hardship in childhood cancer contributes to poor outcomes, no standardized tool to assess its impact exists. Existing methods are heterogeneous and designed using high-income country (HIC), adult perspectives. This project aimed to construct a stakeholder-informed conceptual framework of financial hardship in childhood cancer with global relevancy., Methods: Group concept mapping, a participatory mixed-methods approach, was used. Participants were parents or caregivers of a child with cancer, childhood cancer survivors, and clinical or nonclinical support personnel, fluent in English, Spanish, or Portuguese. A representative panel established a comprehensive list of relevant items. Participants individually sorted these items into concepts and then rated each item for impact using a four-point Likert scale. Multidimensional scaling and hierarchical cluster analysis identified concepts. Descriptive statistics were calculated for impact ratings., Results: One fourth (21/80) of participants were parents/caregivers or childhood cancer survivors. Participants worked in clinical (44/80), charity/volunteer (27/80), and other nonclinical (13/80) roles. Of the 41 represented countries, 78.0% (32) were low- and middle-income countries (LMICs). Conceptual themes spanned six distinct clusters: medical, nonmedical, assistance and support, treatment impact, family impact, and caregiver impact. These were distinct in composition compared with an existing framework for adult oncology. Caregiver impact (mean, 3.39) and treatment impact (mean, 3.29) were the highest rated clusters, and impact ratings were higher in LMICs compared with HICs., Conclusion: We developed a framework for financial hardship in childhood cancer that reflects the voices of stakeholders, including parents and caregivers, from diverse global contexts. The findings lay a foundation for the development and validation of tools to systematically assess financial hardship in families of children with cancer and inform effective policies and interventions.

Background: The aim of this study was to examine some psychometric characteristics of the Chilean-adapted version of the Quantitative Checklist for Autism in Toddlers (Q-CHAT-24) (24) in a group of unselected children (community sample). This version was administered remotely through an online version during the pandemic period to caregivers of children, aged 18-24 months, registered in four primary care polyclinics of the Health Service Araucanía Sur, Chile., Methods: An intentional non-probabilistic sampling was used. Three hundred and thirteen toddlers were examined. Participants completed an online version of the Q-CHAT-24 which was disseminated through the REDCap platform. Evidence of reliability through internal consistency and evidence of predictive validity through ROC curve analysis were realized., Results: The mean age of the children evaluated was 21.16 months. The Shapiro-Wilk test revealed that Q-CHAT-24 scores was normally distributed. 71 cases (23.12%) scored 38 points or more on the Q-CHAT-24, qualifying as Autistic Risk. 48 cases (15.63%) were confirmed as autistic through the ADOS-2 Module T. All items were positively correlated with Q-CHAT-24 total score. All items were positively correlated with Q-CHAT-24 total score. Internal consistency was acceptable for the Q-CHAT-24 (Cronbach ´s α=0.78). The internal consistencies were analyzed for the Q-CHAT-24 Factors, and they were good for factor 1 "Communication and Social Interaction" (Cronbach ´s α=0.85) and acceptable for factor 2 "Restrictive and Repetitive Patterns" (Cronbach ´s α=0.74). Receiver operating characteristic (ROC) curve analyses were performed. The AUC values were 0.93 with statistical significance (p<0.01). For the cut-off point of 38, the Sensitivity, Specificity and Youden index values were 0.89, 0.8 and 0.7, respectively. The Positive Predictive Value (PPV) was 86% and the Negative Predictive Value (NPV) was 85%., Conclusions: In accordance with the objectives of this study, evidence of reliability and predictive validity was demonstrated for the Q-CHAT-24 in this Chilean population. More importantly, this study provides Sensitivity and Specificity data for a remote application version of an autism screening tool already validated in Chile. The implications of this have to do with the possibility of establishing a remote assessment system for children at risk of autism on a population scale., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gatica-Bahamonde, Mendez-Fadol, Sánchez-Sepúlveda, Peñailillo-Diaz, van Kessel, Czabanowska and Roman-Urrestarazu.)

Background: High-quality clinical care requires excellent interdisciplinary communication, especially during emergencies, and no tools exist to evaluate communication in critical care. We describe the development of a pragmatic tool focusing on interdisciplinary communication during patient deterioration (CritCom)., Methods: The preliminary CritCom tool was developed after a literature review and consultation with a multidisciplinary panel of global experts in communication, pediatric oncology, and critical care to review the domains and establish content validity iteratively. Face and linguistic validity were established through cognitive interviews, translation, and linguistic synthesis. We conducted a pilot study among an international group of clinicians to establish reliability and usability., Results: After reviewing 105 potential survey items, we identified 52 items across seven domains. These were refined through cognitive interviews with 36 clinicians from 15 countries. CritCom was piloted with 433 clinicians (58% nurses, 36% physicians, and 6% other) from 42 hospitals in 22 countries. Psychometric testing guided the refinement of the items for the final tool. CritCom comprised six domains with five items each (30 total). The final tool has excellent reliability (Cronbach's alpha 0.81-0.86), usability (93% agree or strongly agree that the tool is easy to use), and similar performance between English and Spanish tools. Confirmatory factor analysis was used to establish the final 6-domain structure., Conclusions: CritCom is a reliable and pragmatic bilingual tool to assess the quality of interdisciplinary communication around patient deterioration for children in diverse resource levels globally. Critcom results can be used to design and evaluate interventions to improve team communication., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rivera, Malone, Puerto-Torres, Prewitt, Counts, Wiphatphumiprates, Sakaan, Al Zebin, Arias, Bhattacharyya, Gunasekera, Johnson, Kambugu, Kaye, Mandrell, Mack, McArthur, Mendez, Morrissey, Sharara-Chami, Snaman, Sniderman, Luke, Graetz and Agulnik.)

Background: Pediatric Early Warning Systems (PEWS) assist early detection of clinical deterioration in hospitalized children with cancer. Relevant to successful PEWS implementation, the "stages of change" model characterizes stakeholder support for PEWS based on willingness and effort to adopt the new practice., Methods: At five resource-limited pediatric oncology centers in Latin America, semi-structured interviews were conducted with 71 hospital staff involved in PEWS implementation. Purposive sampling was used to select centers requiring variable time to complete PEWS implementation, with low-barrier centers (3-4 months) and high-barrier centers (10-11 months). Interviews were conducted in Spanish, professionally transcribed, and translated into English. Thematic content analysis explored "stage of change" with constant comparative analysis across stakeholder types and study sites., Results: Participants identified six interventions (training, incentives, participation, evidence, persuasion, and modeling) and two policies (environmental planning and mandates) as effective strategies used by implementation leaders to promote stakeholder progression through stages of change. Key approaches involved presentation of evidence demonstrating PEWS effectiveness, persuasion and incentives addressing specific stakeholder interests, enthusiastic individuals serving as models for others, and policies enforced by hospital directors facilitating habitual PEWS use. Effective engagement targeted hospital directors during early implementation phases to provide programmatic legitimacy for clinical staff., Conclusion: This study identifies strategies to promote adoption and maintained use of PEWS, highlighting the importance of tailoring implementation strategies to the motivations of each stakeholder type. These findings can guide efforts to implement PEWS and other evidence-based practices that improve childhood cancer outcomes in resource-limited hospitals., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: As implementation science in global health continues to evolve, there is a need for valid and reliable measures that consider diverse linguistic and cultural contexts. A standardized, reproducible process for multilingual measure development may improve accessibility and validity by participants in global health settings. To address this need, we propose a rigorous methodology for multilingual measurement development. We use the example of a novel measure of multi-professional team communication quality, a determinant of implementation efforts., Methods: The development and translation of this novel bilingual measure is comprised of seven steps. In this paper, we describe a measure developed in English and Spanish, however, this approach is not language specific. Participants are engaged throughout the process: first, an interprofessional panel of experts and second, through cognitive interviewing for measure refinement. The steps of measure development included: (1) literature review to identify previous measures of team communication; (2) development of an initial measure by the expert panel; (3) cognitive interviewing in a phased approach with the first language (English); (4): formal, forward-backward translation process with attention to colloquialisms and regional differences in languages; (5) cognitive interviewing repeated in the second language (Spanish); (6) language synthesis to refine both instruments and unify feedback; and (7) final review of the refined measure by the expert panel., Results: A draft measure to assess quality of multi-professional team communication was developed in Spanish and English, consisting of 52 questions in 7 domains. This measure is now ready for psychometric testing., Conclusions: This seven-step, rigorous process of multilingual measure development can be used in a variety of linguistic and resource settings. This method ensures development of valid and reliable tools to collect data from a wide range of participants, including those who have historically been excluded due to language barriers. Use of this method will increase both rigor and accessibility of measurement in implementation science and advance equity in research and practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Malone, Rivera, Puerto-Torres, Prewitt, Sakaan, Counts, Al Zebin, Arias, Bhattacharyya, Gunasekera, Johnson, Kambugu, Kaye, Mandrell, Mack, McArthur, Mendez, Morrissey, Sharara-Chami, Snaman, Sniderman, Luke, Graetz and Agulnik.)

Background: Pediatric Early Warning Systems (PEWS) aid in identification of deterioration in hospitalized children with cancer but are underutilized in resource-limited settings. Proyecto EVAT is a multicenter quality improvement (QI) collaborative in Latin America to implement PEWS. This study investigates the relationship between hospital characteristics and time required for PEWS implementation., Methods: This convergent mixed-methods study included 23 Proyecto EVAT childhood cancer centers; 5 hospitals representing quick and slow implementers were selected for qualitative analysis. Semi-structured interviews were conducted with 71 stakeholders involved in PEWS implementation. Interviews were recorded, transcribed and translated to English, then coded using a priori and novel codes. Thematic content analysis explored the impact of hospital characteristics and QI experience on time required for PEWS implementation and was supplemented by quantitative analysis exploring the relationship between hospital characteristics and implementation time., Results: In both quantitative and qualitative analysis, material and human resources to support PEWS significantly impacted time to implementation. Lack of resources produced various obstacles that extended time necessary for centers to achieve successful implementation. Hospital characteristics, such as funding structure and type, influenced PEWS implementation time by determining their resource-availability. Prior hospital or implementation leader experience with QI, however, helped facilitate implementation by assisting implementers predict and overcome resource-related challenges., Conclusions: Hospital characteristics impact time required to implement PEWS in resource-limited childhood cancer centers; however, prior QI experience helps anticipate and adapt to resource challenges and more quickly implement PEWS. QI training should be a component of strategies to scale-up use of evidence-based interventions like PEWS in resource-limited settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Abutineh, Graetz, Muniz-Talavera, Ferrara, Puerto-Torres, Chen, Gillipelli, Elish, Gonzalez-Ruiz, Alfonso Carreras, Alvarez, Arce Cabrera, Arguello Vargas, Armenta Cruz, Barra, Calderon Sotelo, Carpio, Chavez Rios, Covarrubias, de Leon Vasquez, Diaz Coronado, Fing Soto, Gomez-Garcia, Hernandez, Juarez Tobias, Leon, Loeza Oliva, Mendez, Miller, Montalvo Cozar, Negroe Ocampo, Penafiel, Pineda, Rios, Rodriguez Ordonez, Soto Chavez, Devidas and Agulnik.)

Background: The COVID-19 pandemic impacted healthcare delivery worldwide, including pediatric cancer care, with a disproportionate effect in resource-limited settings. This study evaluates its impact on existing quality improvement (QI) programs., Methods: We conducted 71 semi-structured interviews of key stakeholders at five resource-limited pediatric oncology centers participating in a collaborative to implement Pediatric Early Warning System (PEWS). Interviews were conducted virtually using a structured interview guide, recorded, transcribed, and translated into English. Two coders developed a codebook of a priori and inductive codes and independently coded all transcripts, achieving a kappa of 0.8-0.9. Thematic analysis explored the impact of the pandemic on PEWS., Results: All hospitals reported limitations in material resources, reduction in staffing, and impacts on patient care due to the pandemic. However, the impact on PEWS varied across centers. Identified factors that promoted or limited ongoing PEWS use included the availability of material resources needed for PEWS, staff turnover, PEWS training for staff, and the willingness of staff and hospital leaders to prioritize PEWS. Consequently, some hospitals were able to sustain PEWS; others halted or reduced PEWS use to prioritize other work. Similarly, the pandemic delayed plans at all hospitals to expand PEWS to other units. Several participants were hopeful for future expansion of PEWS post-pandemic., Conclusion: The COVID-19 pandemic created challenges for sustainability and scale of PEWS, an ongoing QI program, in these resource-limited pediatric oncology centers. Several factors mitigated these challenges and promoted ongoing PEWS use. These results can guide strategies to sustain effective QI interventions during future health crises., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Nearly 90% children with cancer reside in low- and middle-income countries, which face multiple challenges delivering high-quality pediatric onco-critical care (POCC). We recently identified POCC quality and capacity indicators for PROACTIVE (PediatRic Oncology cApaCity assessment Tool for IntensiVe carE), a tool that evaluates strengths and limitations in POCC services. This study describes pilot testing of PROACTIVE, development of center-specific reports, and identification of common POCC challenges., Methods: The original 119 consensus-derived PROACTIVE indicators were converted into 182 questions divided between 2 electronic surveys for intensivists and oncologists managing critically ill pediatric cancer patients. Alpha-testing was conducted to confirm face-validity with four pediatric intensivists. Eleven centers representing diverse geographic regions, income levels, and POCC services conducted beta-testing to evaluate usability, feasibility, and applicability of PROACTIVE. Centers' responses were scored and indicators with mean scores ≤75% in availability/performance were classified as common POCC challenges., Results: Alpha-testing ensured face-validity and beta-testing demonstrated feasibility and usability of PROACTIVE (October 2020-June 2021). Twenty-two surveys (response rate 99.4%) were used to develop center-specific reports. Adjustments to PROACTIVE were made based on focus group feedback and surveys, resulting in 200 questions. Aggregated data across centers identified common POCC challenges: (1) lack of pediatric intensivists, (2) absence of abstinence and withdrawal symptoms monitoring, (3) shortage of supportive care resources, and (4) limited POCC training for physicians and nurses., Conclusions: PROACTIVE is a feasible and contextually appropriate tool to help clinicians and organizations identify challenges in POCC services across a wide range of resource-levels. Widespread use of PROACTIVE can help prioritize and develop tailored interventions to strengthen POCC services and outcomes globally., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Communication between providers and patients' families is an integral part of clinical care. Family concern is a validated component of Pediatric Early Warning Systems (PEWS); however, little is known about the impact of PEWS on provider-family communication., Methods: Semi-structured interviews were conducted with 83 ward and Pediatric Intensive Care Unit (PICU) providers involved in the care of patients with deterioration at two pediatric oncology hospitals of different resource levels: St. Jude Children's Research Hospital (n = 42) in the United States and Unidad Nacional de Oncología Pediátrica (UNOP, n = 41) in Guatemala. Interviews were conducted in the participants' native language (English or Spanish), transcribed, and translated into English. Transcripts were coded by two researchers and analyzed for thematic content surrounding family communication and concern., Results: All participants recognized patients' families as a valuable part of the care team, particularly during events requiring escalation of care. Perceived barriers to communication included limited time spent at the bedside, and, at UNOP, language and literacy challenges which occasionally limited providers' ability to assess family concern and involve families in patient care. Despite these barriers, providers perceived PEWS improved communication by facilitating more interaction with families, allowing for relationship-building, anticipatory guidance, and destigmatization of the PICU. PEWS assessments also allowed families to contribute to identification of deterioration., Conclusions: PEWS improve the quality of communication between providers and families by providing more opportunities for interaction, building relationships, and trust. These findings further support the use of PEWS in the care of children with cancer in hospitals of all resource-levels., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Sustainability, or continued use of evidence-based interventions for long-term patient benefit, is the least studied aspect of implementation science. In this study, we evaluate sustainability of a Pediatric Early Warning System (PEWS), an evidence-based intervention to improve early identification of clinical deterioration in hospitalized children, in low-resource settings using the Clinical Capacity for Sustainability Framework (CCS)., Methods: We conducted a secondary analysis of a qualitative study to identify barriers and enablers to PEWS implementation. Semi-structured interviews with PEWS implementation leaders and hospital directors at 5 Latin American pediatric oncology centers sustaining PEWS were conducted virtually in Spanish from June to August 2020. Interviews were recorded, professionally transcribed, and translated into English. Exploratory thematic content analysis yielded staff perceptions on PEWS sustainability. Coded segments were analyzed to identify participant perception about the current state and importance of sustaining PEWS, as well as sustainability successes and challenges. Identified sustainability determinants were mapped to the CCS to evaluate its applicability., Results: We interviewed 71 staff including physicians (45%), nurses (45%), and administrators (10%). Participants emphasized the importance of sustaining PEWS for continued patient benefits. Identified sustainability determinants included supportive leadership encouraging ongoing interest in PEWS, beneficial patient outcomes enhancing perceived value of PEWS, integrating PEWS into the routine of patient care, ongoing staff turnover creating training challenges, adequate material resources to promote PEWS use, and the COVID-19 pandemic. While most identified factors mapped to the CCS, COVID-19 emerged as an additional external sustainability challenge. Together, these challenges resulted in multiple impacts on PEWS sustainment, ranging from a small reduction in PEWS quality to complete disruption of PEWS use and subsequent loss of benefits to patients. Participants described several innovative strategies to address identified challenges and promote PEWS sustainability., Conclusion: This study describes clinician perspectives on sustainable implementation of evidence-based interventions in low-resource settings, including sustainability determinants and potential sustainability strategies. Identified factors mapped well to the CCS, however, external factors, such as the COVID pandemic, may additionally impact sustainability. This work highlights an urgent need for theoretically-driven, empirically-informed strategies to support sustainable implementation of evidence-based interventions in settings of all resource-levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Agulnik, Schmidt-Grimminger, Ferrara, Puerto-Torres, Gillipelli, Elish, Muniz-Talavera, Gonzalez-Ruiz, Armenta, Barra, Diaz-Coronado, Hernandez, Juarez, Loeza, Mendez, Montalvo, Penafiel, Pineda, Graetz and McKay.)

Background: Pediatric Early Warning Systems (PEWS) reduce clinical deterioration, improve interdisciplinary communication, and provide cost savings; however, little is known about how these impacts are achieved or related. This study evaluates the multi-level impacts of PEWS in resource-limited pediatric oncology centers., Methods: We conducted 71 semi-structured interviews including physicians (45%), nurses (45%), and administrators (10%) from 5 resource-limited pediatric oncology centers in 4 Latin American countries. Interviews were conducted in Spanish, transcribed, and translated into English. A code book was developed using a priori and inductively derived codes. Transcripts were independently coded by 2 coders, achieving a kappa of 0.8-0.9. Thematic content analysis explored perceived impacts of PEWS at the level of the patient , clinician , healthcare team , and institution ., Results: PEWS improved the quality of attention for patients , reducing morbidity and mortality. Clinicians felt more knowledgeable, confident, and empowered providing patient care, resulting in greater job satisfaction. PEWS affected team dynamics by improving interdisciplinary (ward and intensive care unit) and interprofessional (physicians and nurses) relationships and communication. This ultimately led to institutional culture change with emphasis on patient safety, collaboration with other centers, and receipt of institutional awards. Together, these impacts led to hospital-wide support of ongoing PEWS use., Conclusions: In resource-limited hospitals, PEWS use results in multi-level positive impacts on patients , clinicians , teams , and institutions , creating a feedback loop that further supports ongoing PEWS use. These findings can guide advocacy for PEWS to various stakeholders, improve PEWS effectiveness, and inform assessment of other interventions to improve childhood cancer outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mirochnick, Graetz, Ferrara, Puerto-Torres, Gillipelli, Elish, Muniz-Talavera, Gonzalez-Ruiz, Armenta, Barra, Diaz-Coronado, Hernandez, Juarez, Loeza, Mendez, Montalvo, Penafiel, Pineda and Agulnik.)

Importance: Pediatric early warning systems (PEWS) aid with early identification of clinical deterioration and improve outcomes in children with cancer hospitalized in resource-limited settings; however, there may be barriers to implementation., Objective: To evaluate stakeholder-reported barriers and enablers to PEWS implementation in resource-limited hospitals., Design, Setting, and Participants: In this qualitative study, semistructured stakeholder interviews were conducted at 5 resource-limited pediatric oncology centers in 4 countries in Latin America. Hospitals participating in a multicenter collaborative to implement PEWS were purposefully sampled based on time required for implementation (fast vs slow), and stakeholders interviewed included physicians, nurses, and administrators, involved in PEWS implementation. An interview guide was developed using the Consolidated Framework for Implementation Research (CFIR). Interviews were conducted virtually in Spanish, audiorecorded, and professionally transcribed and translated into English. A codebook was developed a priori using the CFIR and supplemented with codes inductively derived from transcript review. Two coders independently analyzed all transcripts, achieving a κ of 0.8 to 0.9. The study was conducted from June 1 to August 31, 2020., Main Outcomes and Measures: Thematic analysis was conducted based on CFIR domains (inner setting, characteristics of individuals, outer setting, intervention characteristics, and implementation process) to identify barriers and enablers to PEWS implementation., Results: Seventy-one staff involved in PEWS implementation were interviewed, including 32 physicians (45%), 32 nurses (45%), and 7 administrators (10%). Of these, 50 were women (70%). Components of the 5 CFIR domains were mentioned by participants as barriers and enablers to PEWS implementation at both fast- and slow-implementing centers. Participants emphasized barriers at the level of the clinical staff, hospital, external factors, and PEWS intervention. These barriers included staff resistance to change, inadequate resources, components of health systems, and the perceived origin and complexity of PEWS. At all centers, most barriers were successfully converted to enablers during the implementation process through targeted strategies, such as early stakeholder engagement and adaptation, including adapting PEWS to better fit the local context and changing the hospital setting to support ongoing use of PEWS., Conclusions and Relevance: To date, this is the first multicenter, multinational study describing barriers and enablers to PEWS implementation in resource-limited settings. Findings suggest that many barriers are not immutable and can be converted to enablers during the implementation process. This work can serve as a guide for clinicians looking to implement evidence-based interventions to reduce global disparities in patient outcomes.