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 PARTICIPANTSIn 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. RESULTSSeventy-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 RELEVANCETo 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 (continued) Key Points Question What barriers and enablers to pediatric early warning systems (PEWS) implementation in resource-limited hospitals are reported by health care professionals? Findings In this qualitative study including 5 resource-limited pediatric oncology centers in 4 countries in Latin America, ma...

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The lateral septum (LS) is a limbic nucleus interconnected with several brain areas involved in the regulation of mood and reward. Vasopressin (AVP) is a neuropeptide that has been related to the effects of drugs of abuse, but its role in the addictive process is poorly understood. LS expresses a high density of AVP 1A receptors (V 1A). The aim of this work was to examine whether the modulation of LS AVP system affects the behavioral and neurochemical responses to amphetamine (AMPH) in male rats. Our results show that AMPH-induced conditioned place preference (CPP) produces a decrease in LS AVP content. Besides, we demonstrate that the microinjection of AVP in the LS impairs the expression of AMPH-induced CPP and that this effect is mediated by the activation of the V 1A receptor in the LS. AVP microinjection in the LS elicited a decrease in neuronal activity in the nucleus accumbens (NAc) in animals subjected to AMPH conditioning. Finally, AVP microinjection in the LS decreased dopamine (DA) release in the NAc. Overall, our data demonstrate that intra-LS AVP diminishes the expression of AMPH conditioning behavior while decreasing neuronal activity and DA release in the NAc. Presumably, the effects of AVP in the LS produce an inhibition of GABAergic projections to the VTA, increasing local inhibitory tone in this nucleus, which in turn reduces the activity of DA projections to NAc. Thus, these results contribute to the knowledge about the role of AVP in LS in regulating the reward circuit and addictive like behaviors.

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.

Tacrolimus bioavailability in steady state is similar in BID and QD formulations after conversion in stable LT recipients, excluding those with cystic fibrosis. Thus, our results indicate TAC BID can be safely switched to the more convenient QD formulation in this population.