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.
BackgroundPaediatric Early Warning Systems (PEWSs) improve identification of deterioration, however, their sustainability has not been studied. Sustainability is critical to maximise impact of ...interventions like PEWS, particularly in low-resource settings. This study establishes the reliability and validity of a Spanish-language Clinical Sustainability Assessment Tool (CSAT) to assess clinical capacity to sustain interventions in resource-limited hospitals.MethodsParticipants included PEWS implementation leadership teams of 29 paediatric cancer centres in Latin America involved in a collaborative to implement PEWS. The CSAT, a sustainability assessment tool validated in high-resource settings, was translated into Spanish and distributed to participants as an anonymous electronic survey. Psychometric, confirmatory factor analysis (CFA), and multivariate analyses were preformed to assess reliability, structure and initial validity. Focus groups were conducted after participants reviewed CSAT reports to assess their interpretation and utility.ResultsThe CSAT survey achieved an 80% response rate (n=169) with a mean score of 4.4 (of 5; 3.8–4.8 among centres). The CSAT had good reliability with an average internal consistency of 0.77 (95% CI 0.71 to 0.81); and CFAs supported the seven-domain structure. CSAT results were associated with respondents’ perceptions of the evidence for PEWS, its implementation and use in their centre, and their assessment of the hospital culture and implementation climate. The mean CSAT score was higher among respondents at centres with longer time using PEWS (p<0.001). Focus group participants noted the CSAT report helped assess their centre’s clinical capacity to sustain PEWS and provided constructive feedback for improvement.ConclusionsWe present information supporting the reliability and validity of the CSAT tool, the first Spanish-language instrument to assess clinical capacity to sustain evidence-based interventions in hospitals of variable resource levels. This assessment demonstrates a high capacity to sustain PEWS in these resource-limited centres with improvement over time from PEWS implementation.
Immune response to a given antigen, particularly in cancer patients, is complex and is controlled by various genetic and environmental factors. Identifying biomarkers that can predict robust response ...to immunization is an urgent need in clinical cancer vaccine development. Given the involvement of DNA methylation in the development of lymphocytes, tumorigenicity and tumor progression, we aimed to analyze pre-vaccination DNA methylation profiles of peripheral blood mononuclear cells (PBMCs) from breast cancer subjects vaccinated with a novel peptide-based vaccine referred to as P10s-PADRE. This pilot study was performed to evaluate whether signatures of differentially methylated (DM) loci can be developed as potential predictive biomarkers for prescreening subjects with cancer who will most likely generate an immune response to the vaccine. Genomic DNA was isolated from PBMCs of eight vaccinated subjects, and their DNA methylation profiles were determined using Infinium
®
MethylationEPIC BeadChip array from Illumina. A linear regression model was applied to identify loci that were differentially methylated with respect to anti-peptide antibody titers and with IFN-γ production. The data were summarized using unsupervised-learning methods: hierarchical clustering and principal-component analysis. Pathways and networks involved were predicted by Ingenuity Pathway Analysis. We observed that the profile of DM loci separated subjects in regards to the levels of immune responses. Canonical pathways and networks related to metabolic and immunological functions were found to be involved. The data suggest that it is feasible to correlate methylation signatures in pre-treatment PBMCs with immune responses post-treatment in cancer patients going through standard-of-care chemotherapy. Larger and prospective studies that focus on DM loci in PBMCs is warranted to develop pre-screening biomarkers before BC vaccination.
Clinical Trial Registration:
www.ClinicalTrials.gov
, Identifier: NCT02229084.
Dual-organelle molecular localizers represent powerful new tools allowing the exploration of interorganelle physical contacts and subcellular chemical communication. Here, we describe new dynamic ...molecular probes to localize mitochondria and lipid droplets taking advantage of the differential proton gradients present in these organelles as well as the activity of mitochondrial esterase. We unveil their potential utility when organelle retention mechanisms and proton gradients are synchronized, an insight that has not been documented previously. Our discoveries indicate that dual-organelle probes serve as a valuable multiplexing assay during starvation-induced autophagy. The pioneering molecular mechanism they employ opens doors to avoid using labile esters such as acetoxymethyl derivatives which are not optimal in imaging microscopy assays.
A growing wealth of data suggest that reactive oxygen species (ROS) signalling might be crucial in conferring embryonic or adult stem cells their specific properties. However, how stem cells control ...ROS production and scavenging, and how ROS in turn contribute to stemness, remain poorly understood. Using the Xenopus retina as a model system, we first investigated the redox status of retinal stem cells (RSCs). We discovered that they exhibit higher ROS levels compared with progenitors and retinal neurons, and express a set of specific redox genes. We next addressed the question of ROS functional involvement in these cells. Using pharmacological or genetic tools, we demonstrate that inhibition of NADPH oxidase-dependent ROS production increases the proportion of quiescent RSCs. Surprisingly, this is accompanied by an apparent acceleration of the mean division speed within the remaining proliferating pool. Our data further unveil that such impact on RSC cell cycling is achieved by modulation of the Wnt/Hedgehog signalling balance. Altogether, we highlight that RSCs exhibit distinctive redox characteristics and exploit NADPH oxidase signalling to limit quiescence and fine-tune their proliferation rate.
The reaction by melt mixing at 220 °C of the antihyperglycemic drug metformin hydrochloride 1 with dehydrated sodium succinate yields efficiently the organic salt MET2SUC 2 (H-MET+= metforminium and ...SUC2- = succinate). Solid state CPMAS NMR 13C spectroscopy experiments, powder X-ray diffraction and FT-IR results support the formation of the pharmaceutical salt 2 in good yields. Besides, the charged-assisted hydrogen bonding interactions of type N-H…-O(carboxylate) were thoroughly analyzed by single crystal X-Ray diffraction techniques. Thus, the pharmaceutical salt 2 possesses considerable thermal differences when compared to the pure starting reagents. In addition, intrinsic dissolution rate experiments in buffered aqueous solutions at pH= 6.8 showed a sustained-release behavior of the drug in 2 with a constant value of Kint = 0.885 mg/min * cm2.
The current study examined the role of stimulus combinations on the repeated assessment of resurgence. Using a within-session resurgence procedure, rats were exposed to different conditions, each ...with distinct stimulus combinations (AAA, ABA, ABB, ABC and AAB). Two arrangements of stimulus changes were compared: Experiment 1 involved changes in stimulus combinations every five sessions, while Experiment 2 implemented changes every session. Resurgence was observed in both experiments; however, Experiment 2 demonstrated more consistent and repeated resurgence when stimulus combinations changed every session. Notably, the ABA, ABB and ABC conditions showed the highest percentage of sessions in which resurgence was observed. Lastly, the current study extends the application of the within-session resurgence procedure to rats and auditory stimuli, providing a reliable method for assessing resurgence in single subjects under different variable conditions.
•Resurgence was repeatedly observed in rats using a within-session procedure.•Different stimulus combinations resulted on varying levels of resurgence.•Daily changes in stimulus combination allowed for repeated resurgence.•Resurgence consistently decreased as subjects were repeatedly exposed to each test.
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.
The COVID‐19 pandemic created challenges to maintain and scale‐up an ongoing quality improvement initiative, a Pediatric Early Warning System (PEWS), in five pediatric oncology hospitals in Latin America. Identified factors mitigate these challenges and promote ongoing PEWS use can be leveraged to support sustainability of programs to reduce global disparities in childhood cancer during future health crises.
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.
This multicenter, multinational qualitative study identifies strategies used by implementation leaders to promote hospital staff's decision to adopt a Pediatric Early Warning System (PEWS) in resource‐limited pediatric oncology centers. These findings can guide efforts to implement PEWS and other quality improvement tools that improve childhood cancer outcomes globally.
Subcellular microenvironment plays a crucial role in maintaining cell homeostasis being hydration an essential parameter to monitor the variations of lipid organization in biological membranes. ...Fluorescent microenvironment‐sensitive probes are stimuli‐responsive molecules and able to change their fluorescence profile according to the microenvironment properties (polarity, hydration, microviscosity and tension). Here we present an organic fluorescent probe, NPM‐1, as a new microenvironmental dye with selective plasma membrane localization in live cells. Using high‐resolution confocal microscopy and fluorescence spectroscopy, we explored the hydration and polarity variations during the formation of apoptotic bodies in real time. To have a clear understanding of the cell microenvironment variations, an analogue polarity probe able to localize the cytosol and nucleoli was also synthetized, CellPol‐1. Then, we were able to monitor the subcellular hydration variations during the apoptotic body dynamics.
Two fluorescent probes are reported to detect plasma membrane hydration in cells under homeostatic and apoptotic conditions through an integrated dual‐color bioanalytical protocol.
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