Bilateral remote ischemic conditioning in children: A two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgery.

Objective: The study objective was to determine whether adequately delivered bilateral remote ischemic preconditioning is cardioprotective in young children undergoing surgery for 2 common congenital heart defects with or without cyanosis. Methods: We performed a prospective, double-blind, randomized controlled trial at 2 centers in the United Kingdom. Children aged 3 to 36 months undergoing tetralogy of Fallot repair or ventricular septal defect closure were randomized 1:1 to receive bilateral preconditioning or sham intervention. Participants were followed up until hospital discharge or 30 days. The primary outcome was area under the curve for high-sensitivity troponin-T in the first 24 hours after surgery, analyzed by intention-to-treat. Right atrial biopsies were obtained in selected participants. Results: Between October 2016 and December 2020, 120 eligible children were randomized to receive bilateral preconditioning (n = 60) or sham intervention (n = 60). The primary outcome, area under the curve for high-sensitivity troponin-T, was higher in the preconditioning group (mean: 70.0 ± 50.9 µg/L/h, n = 56) than in controls (mean: 55.6 ± 30.1 µg/L/h, n = 58) (mean difference, 13.2 µg/L/h; 95% CI, 0.5-25.8; P = .04). Subgroup analyses did not show a differential treatment effect by oxygen saturations (pinteraction = .25), but there was evidence of a differential effect by underlying defect (pinteraction = .04). Secondary outcomes and myocardial metabolism, quantified in atrial biopsies, were not different between randomized groups. Conclusions: Bilateral remote ischemic preconditioning does not attenuate myocardial injury in children undergoing surgical repair for congenital heart defects, and there was evidence of potential harm in unstented tetralogy of Fallot. The routine use of remote ischemic preconditioning cannot be recommended for myocardial protection during pediatric cardiac surgery.

The development and validation of the One Health Community Assessment.

Interdisciplinary collaborations to address human, animal, and environmental health have been emphasized since the inception of the One Health framework. A quantitative survey instrument was developed to measure perceptions of the impacts of pets on One Health. Using the exploratory sequential mixed methods approach, 20 interviews were conducted with individuals from a racially diverse and low-socioeconomic status community in the U.S. to understand their perceptions of One Health. Data from those interviews informed the development of a Likert scale survey measuring individual perceptions of community, human, pet, and environmental health and welfare, as well as the connections between the domains of the One Health triad (human, animal, and environment). The resulting One Health Community Assessment (OHCA) was administered in two urban and two rural underserved U.S. communities longitudinally (2018-2021) through door-to-door data collection as well as phone, email, and text surveys. Validation of the instrument was completed using data collected in the third and fourth years of the study (n = 654). Factor analysis with orthogonal varimax rotation was used to assess the structure and internal consistency of the OHCA. Five subscales explained 42.4% of the variance in our 92-item instrument: community health (Cronbach's α = 0.897), human health (α = 0.842), pet health (α = 0.899), environmental health (α = 0.789), and connections between domains of One Health (α = 0.762). The OHCA represents the first reliable and validated instrument to measure the impacts of pets on One Health.

Extracellular Vesicles Loaded with Long Antisense RNAs Repress Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Long antisense RNAs (asRNAs) have been observed to repress HIV and other virus expression in a manner that is refractory to viral evolution. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) disease, has a distinct ability to evolve resistance around antibody targeting, as was evident from the emergence of various SARS-CoV-2 spike antibody variants. Importantly, the effectiveness of current antivirals is waning due to the rapid emergence of new variants of concern, more recently the omicron variant. One means of avoiding the emergence of viral resistance is by using long asRNA to target SARS-CoV-2. Similar work has proven successful with HIV targeting by long asRNA. In this study, we describe a long asRNA targeting SARS-CoV-2 RNA-dependent RNA polymerase gene and the ability to deliver this RNA in extracellular vesicles (EVs) to repress virus expression. The observations presented in this study suggest that EV-delivered asRNAs are one means to targeting SARS-CoV-2 infection, which is both effective and broadly applicable as a means to control viral expression in the absence of mutation. This is the first demonstration of the use of engineered EVs to deliver long asRNA payloads for antiviral therapy.

Therapeutic potential of RNA-enriched extracellular vesicles: The next generation in RNA delivery via biogenic nanoparticles.

Exosomes are extracellular vesicles (EVs) (∼50-150 nm) that have emerged as promising vehicles for therapeutic applications and drug delivery. These membrane-bound particles, released by all actively dividing cells, have the ability to transfer effector molecules, including proteins, RNA, and even DNA, from donor cells to recipient cells, thereby modulating cellular responses. RNA-based therapeutics, including microRNAs, messenger RNAs, long non-coding RNAs, and circular RNAs, hold great potential in controlling gene expression and treating a spectrum of medical conditions. RNAs encapsulated in EVs are protected from extracellular degradation, making them attractive for therapeutic applications. Understanding the intricate biology of cargo loading and transfer within EVs is pivotal to unlocking their therapeutic potential. This review discusses the biogenesis and classification of EVs, methods for loading RNA into EVs, their advantages as drug carriers over synthetic-lipid-based systems, and the potential applications in treating neurodegenerative diseases, cancer, and viral infections. Notably, EVs show promise in delivering RNA cargo across the blood-brain barrier and targeting tumor cells, offering a safe and effective approach to RNA-based therapy in these contexts.

An intranasally delivered ultra-conserved siRNA prophylactically represses SARS-CoV-2 infection in the lung and nasal cavity.

There remains a striking overall mortality burden of COVID-19 worldwide. Given the waning effectiveness of current SARS-CoV-2 antivirals due to the rapid emergence of new variants of concern (VOC), we employed a direct-acting molecular therapy approach using gene silencing RNA interference (RNAi) technology. In this study, we developed and screened several ultra-conserved small-interfering RNAs (siRNAs) before selecting one potent siRNA candidate for pre-clinical in vivo testing. This non-immunostimulatory, anti-SARS-CoV-2 siRNA candidate maintains its antiviral activity against all tested SARS-CoV-2 VOC and works effectively as a single agent. For the first time, significant antiviral effects in both the lungs and nasal cavities of SARS-CoV-2 infected mice were observed when this siRNA candidate was delivered intranasally (IN) as a prophylactic agent with the aid of lipid nanoparticles (LNPs). Importantly, a pre-exposure prophylactic IN-delivered anti-SARS-CoV-2 siRNA antiviral that can ameliorate viral replication in the nasal cavity could potentially prevent aerosol spread of respiratory viruses. An IN delivery approach would allow for the development of a direct-acting nasal spray approach that could be self-administered prophylactically.

Implementing early rehabilitation and mobilisation for children in UK paediatric intensive care units: the PERMIT feasibility study.

Background: Early rehabilitation and mobilisation encompass patient-tailored interventions, delivered within intensive care, but there are few studies in children and young people within paediatric intensive care units. Objectives: To explore how healthcare professionals currently practise early rehabilitation and mobilisation using qualitative and quantitative approaches; co-design the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual of early rehabilitation and mobilisation interventions, with primary and secondary patient-centred outcomes; explore feasibility and acceptability of implementing the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual within three paediatric intensive care units. Design: Mixed-methods feasibility with five interlinked studies (scoping review, survey, observational study, codesign workshops, feasibility study) in three phases. Setting: United Kingdom paediatric intensive care units. Participants: Children and young people aged 0-16 years remaining within paediatric intensive care on day 3, their parents/guardians and healthcare professionals. Interventions: In Phase 3, unit-wide implementation of manualised early rehabilitation and mobilisation. Main outcome measures: Phase 1 observational study: prevalence of any early rehabilitation and mobilisation on day 3. Phase 3 feasibility study: acceptability of early rehabilitation and mobilisation intervention; adverse events; acceptability of study design; acceptability of outcome measures. Data sources: Searched Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature, MEDLINE, PEDro, Open grey and Cochrane CENTRAL databases. Review methods: Narrative synthesis. Results: In the scoping review we identified 36 full-text reports evaluating rehabilitation initiated within 7 days of paediatric intensive care unit admission, outlining non-mobility and mobility early rehabilitation and mobilisation interventions from 24 to 72 hours and delivered twice daily. With the survey, 124/191 (65%) responded from 26/29 (90%) United Kingdom paediatric intensive care units; the majority considered early rehabilitation and mobilisation a priority. The observational study followed 169 patients from 15 units; prevalence of any early rehabilitation and mobilisation on day 3 was 95.3%. We then developed a manualised early rehabilitation and mobilisation intervention informed by current evidence, experience and theory. All three sites implemented the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual successfully, recruited to target (30 patients recruited) and followed up the patients until day 30 or discharge; 21/30 parents consented to complete additional outcome measures. Limitations: The findings represent the views of National Health Service staff but may not be generalisable. We were unable to conduct workshops and interviews with children, young people and parents to support the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual development due to pandemic restrictions. Conclusions: A randomised controlled trial is recommended to assess the effectiveness of the manualised early rehabilitation and mobilisation intervention. Future work: A definitive cluster randomised trial of early rehabilitation and mobilisation in paediatric intensive care requires selection of outcome measure and health economic evaluation. Study registration: The study is registered as PROSPERO CRD42019151050. The Phase 1 observational study is registered Clinicaltrials.gov NCT04110938 (Phase 1) (registered 1 October 2019) and the Phase 3 feasibility study is registered NCT04909762 (Phase 3) (registered 2 June 2021). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/21/06) and is published in full in Health Technology Assessment; Vol. 27, No. 27. See the NIHR Funding and Awards website for further award information.

Early rehabilitation and mobilisation, within the first week of intensive care admission, can improve the speed of recovery from illness or injury in adults. However, there is a lack of evidence about whether critically unwell children benefit from early rehabilitation and mobilisation. We aimed to identify which patients may benefit from early rehabilitation and mobilisation. Also, to develop and test a manual of early rehabilitation and mobilisation using the best evidence and expertise ­ called the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual. Then evaluate whether the manual could be implemented safely in paediatric intensive care units and was acceptable to staff and families. We undertook in respect of early rehabilitation and mobilisation: review of existing research; national survey of practice (124 staff); gathered information about current conduct (15 paediatric intensive care units, 169 patients); spoke to experts (18 people); developed the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual to guide paediatric intensive care unit staff; Tested the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual in three paediatric intensive care units with 30 patients; gathered feedback from healthcare professionals via weekly 'debriefs' (47), interviews (13) and surveys (118), and from parents via parent-completed questionnaires (21) and interviews (14). Despite being regarded as important, currently early rehabilitation and mobilisation practice is inconsistent, not considered 'early' enough and often focuses on low-risk activities conducted on the bed. Introducing the Paediatric Early Rehabilitation and Mobilisation during InTensive care manual as part of a trial was acceptable and feasible and helps standardise delivery to unwell children. Measuring child and parent reported outcomes was acceptable but follow-up at 30 days was incomplete. A larger trial of early rehabilitation and mobilisation, involving more paediatric intensive care units, is feasible and required to demonstrate benefit to children.

Delivery of a novel intervention to facilitate liberation from mechanical ventilation in paediatric intensive care: A process evaluation.

BACKGROUND: Prolonged mechanical ventilation increases the risk of mortality and morbidity. Optimising sedation and early testing for possible liberation from invasive mechanical ventilation (IMV) has been shown to reduce time on the ventilator. Alongside a multicentre trial of sedation and ventilation weaning, we conducted a mixed method process evaluation to understand how the intervention content and delivery was linked to trial outcomes. METHODS: 10,495 children admitted to 18 paediatric intensive care units (ICUs) in the United Kingdom participated in a stepped-wedge, cluster randomised controlled trial, with 1955 clinical staff trained to deliver the intervention. The intervention comprised assessment and optimisation of sedation levels, and bedside screening of respiratory parameters to indicate readiness for a spontaneous breathing trial prior to liberation from ventilation. 193 clinical staff were interviewed towards the end of the trial. Interview data were thematically analysed, and quantitative adherence data were analysed using descriptive statistics. RESULTS: The intervention led to a reduced duration of IMV (adjusted median difference- 7.1 hours, 95% CI -9.6 to -5.3, p = 0.01). Overall intervention adherence was 75% (range 59-85%). Ease and flexibility of the intervention promoted it use; designated responsibilities, explicit pathways of decision-making and a shared language for communication fostered proactivity and consistency towards extubation. Delivery of the intervention was hindered by established hospital and unit organisational and patient care routines, clinician preference and absence of clinical leadership. CONCLUSIONS: The SANDWICH trial showed a significant, although small, reduction in duration of IMV. Findings suggest that greater direction in decision-making pathways, robust embedment of new practice in unit routine, and capitalising on the skills of Advanced Nurse Practitioners and physiotherapists would have contributed to greater intervention effect. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN16998143.

A latent scale model to minimize subjectivity in the analysis of visual rating data for the National Turfgrass Evaluation Program.

Introduction: Traditional evaluation procedure in National Turfgrass Evaluation Program (NTEP) relies on visually assessing replicated turf plots at multiple testing locations. This process yields ordinal data; however, statistical models that falsely assume these to be interval or ratio data have almost exclusively been applied in the subsequent analysis. This practice raises concerns about procedural subjectivity, preventing objective comparisons of cultivars across different test locations. It may also lead to serious errors, such as increased false alarms, failures to detect effects, and even inversions of differences among groups. Methods: We reviewed this problem, identified sources of subjectivity, and presented a model-based approach to minimize subjectivity, allowing objective comparisons of cultivars across different locations and better monitoring of the evaluation procedure. We demonstrate how to fit the described model in a Bayesian framework with Stan, using datasets on overall turf quality ratings from the 2017 NTEP Kentucky bluegrass trials at seven testing locations. Results: Compared with the existing method, ours allows the estimation of additional parameters, i.e., category thresholds, rating severity, and within-field spatial variations, and provides better separation of cultivar means and more realistic standard deviations. Discussion: To implement the proposed model, additional information on rater identification, trial layout, rating date is needed. Given the model assumptions, we recommend small trials to reduce rater fatigue. For large trials, ratings can be conducted for each replication on multiple occasions instead of all at once. To minimize subjectivity, multiple raters are required. We also proposed new ideas on temporal analysis, incorporating existing knowledge of turfgrass.

Corrigendum: Examining human-animal interactions and their effect on multidimensional frailty in later life: a scoping review.

[This corrects the article DOI: 10.3389/fpubh.2023.1214127.].

Examining human-animal interactions and their effect on multidimensional frailty in later life: a scoping review.

This scoping review sought to compile outcomes associated with any human-animal interaction study regarding adults aged 50 and older in any living context and concerning a multidimensional (i.e., physical, psychological, cognitive, and social) perspective of frailty. Despite our best attempts at incorporating the broadest inclusion criteria possible, only four articles were relevant to this review. Participants across the included studies were rural, community-dwelling Japanese or Chinese individuals aged 60 years and older. Thematic analysis of reported results includes dog ownership as a protective factor regarding frailty, the interconnected health effects of pet ownership, and increased meaning and purpose through pet ownership implications. More research is needed globally to determine how human-animal interactions may moderate frailty comprehensively, as well as the efficacy and appropriateness of these interactions or interventions in older adult populations and across cultural boundaries.

Evaluation of the Elements of Short Hairpin RNAs in Developing shRNA-Containing CAR T Cells.

Short hairpin RNAs (shRNAs) have emerged as a powerful tool for gene knockdown in various cellular systems, including chimeric antigen receptor (CAR) T cells. However, the elements of shRNAs that are crucial for their efficacy in developing shRNA-containing CAR T cells remain unclear. In this study, we evaluated the impact of different shRNA elements, including promoter strength, orientation, multiple shRNAs, self-targeting, and sense and antisense sequence composition on the knockdown efficiency of the target gene in CAR T cells. Our findings highlight the importance of considering multiple shRNAs and their orientation to achieve effective knockdown. Moreover, we demonstrate that using a strong promoter and avoiding self-targeting can enhance CAR T cell functionality. These results provide a framework for the rational design of CAR T cells with shRNA-mediated knockdown capabilities, which could improve the therapeutic efficacy of CAR T cell-based immunotherapy.

Mandan, Hidatsa, and Arikara Nation Perspectives on Rez Dogs on the Fort Berthold Reservation in North Dakota, U.S.A.

The research on the relationships between free-roaming dogs, also referred to as reservation dogs or rez dogs, and Indigenous communities is extremely limited. This study aimed to document the cultural significance of rez dogs, challenges related to rez dogs, and community-specific solutions for rez dog issues affecting community health and safety from members of the Mandan, Hidatsa, and Arikara (MHA) Nation, also referred to as the Three Affiliated Tribes (TAT), who live on the Fort Berthold reservation in North Dakota, U.S.A. One hour semi-structured interviews with 14 community members of the MHA Nation were conducted in 2016. The interviews were analyzed via systematic and inductive coding using Gadamer's hermeneutical phenomenology. The primary intervention areas described by the participants included: culturally relevant information sharing, improved animal control policies and practices, and improved access to veterinary care and other animal services.

Prophylactic intranasal administration of lipid nanoparticle formulated siRNAs reduce SARS-CoV-2 and RSV lung infection.

RNA interference (RNAi) is an emerging and promising therapy for a wide range of respiratory viral infections. This highly specific suppression can be achieved by the introduction of short-interfering RNA (siRNA) into mammalian systems, resulting in the effective reduction of viral load. Unfortunately, this has been hindered by the lack of a good delivery system, especially via the intranasal (IN) route. Here, we have developed an IN siRNA encapsulated lipid nanoparticle (LNP) in vivo delivery system that is highly efficient at targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV) lung infection in vivo. Importantly, IN siRNA delivery without the aid of LNPs abolishes anti-SARS-CoV-2 activity in vivo. Our approach using LNPs as the delivery vehicle overcomes the significant barriers seen with IN delivery of siRNA therapeutics and is a significant advancement in our ability to delivery siRNAs. The study presented here demonstrates an attractive alternate delivery strategy for the prophylactic treatment of both future and emerging respiratory viral diseases.

The Infant KIdney Dialysis and Utrafiltration (I-KID) Study: A Stepped-Wedge Cluster-Randomized Study in Infants, Comparing Peritoneal Dialysis, Continuous Venovenous Hemofiltration, and Newcastle Infant Dialysis Ultrafiltration System, a Novel Infant Hemodialysis Device.

OBJECTIVES: Renal replacement therapy (RRT) options are limited for small babies because of lack of available technology. We investigated the precision of ultrafiltration, biochemical clearances, clinical efficacy, outcomes, and safety profile for a novel non-Conformité Européenne-marked hemodialysis device for babies under 8 kg, the Newcastle Infant Dialysis Ultrafiltration System (NIDUS), compared with the current options of peritoneal dialysis (PD) or continuous venovenous hemofiltration (CVVH). DESIGN: Nonblinded cluster-randomized cross-sectional stepped-wedge design with four periods, three sequences, and two clusters per sequence. SETTING: Clusters were six U.K. PICUs. PATIENTS: Babies less than 8 kg requiring RRT for fluid overload or biochemical disturbance. INTERVENTIONS: In controls, RRT was delivered by PD or CVVH, and in interventions, NIDUS was used. The primary outcome was precision of ultrafiltration compared with prescription; secondary outcomes included biochemical clearances. MEASUREMENTS AND MAIN RESULTS: At closure, 97 participants were recruited from the six PICUs (62 control and 35 intervention). The primary outcome, obtained from 62 control and 21 intervention patients, showed that ultrafiltration with NIDUS was closer to that prescribed than with control: sd controls, 18.75, intervention, 2.95 (mL/hr); adjusted ratio, 0.13; 95% CI, 0.03-0.71; p = 0.018. Creatinine clearance was smallest and least variable for PD (mean, sd ) = (0.08, 0.03) mL/min/kg, larger for NIDUS (0.46, 0.30), and largest for CVVH (1.20, 0.72). Adverse events were reported in all groups. In this critically ill population with multiple organ failure, mortality was lowest for PD and highest for CVVH, with NIDUS in between. CONCLUSIONS: NIDUS delivers accurate, controllable fluid removal and adequate clearances, indicating that it has important potential alongside other modalities for infant RRT.

Targeted zinc-finger repressors to the oncogenic HBZ gene inhibit adult T-cell leukemia (ATL) proliferation.

Human T-lymphotropic virus type I (HTLV-I) infects CD4+ T-cells resulting in a latent, life-long infection in patients. Crosstalk between oncogenic viral factors results in the transformation of the host cell into an aggressive cancer, adult T-cell leukemia/lymphoma (ATL). ATL has a poor prognosis with no currently available effective treatments, urging the development of novel therapeutic strategies. Recent evidence exploring those mechanisms contributing to ATL highlights the viral anti-sense gene HTLV-I bZIP factor (HBZ) as a tumor driver and a potential therapeutic target. In this work, a series of zinc-finger protein (ZFP) repressors were designed to target within the HTLV-I promoter that drives HBZ expression at highly conserved sites covering a wide range of HTLV-I genotypes. ZFPs were identified that potently suppressed HBZ expression and resulted in a significant reduction in the proliferation and viability of a patient-derived ATL cell line with the induction of cell cycle arrest and apoptosis. These data encourage the development of this novel ZFP strategy as a targeted modality to inhibit the molecular driver of ATL, a possible next-generation therapeutic for aggressive HTLV-I associated malignancies.

Extracellular vesicles: The next generation in gene therapy delivery.

Extracellular vesicles (EVs) are esteemed as a promising delivery vehicle for various genetic therapeutics. They are relatively inert, non-immunogenic, biodegradable, and biocompatible. At least in rodents, they can even transit challenging bodily hurdles such as the blood-brain barrier. Constitutively shed by all cells and with the potential to interact specifically with neighboring and distant targets, EVs can be engineered to carry and deliver therapeutic molecules such as proteins and RNAs. EVs are thus emerging as an elegant in vivo gene therapy vector. Deeper understanding of basic EV biology-including cellular production, EV loading, systemic distribution, and cell delivery-is still needed for effective harnessing of these endogenous cellular nanoparticles as next-generation nanodelivery tools. However, even a perfect EV product will be challenging to produce at clinical scale. In this regard, we propose that vector transduction technologies can be used to convert cells either ex vivo or directly in vivo into EV factories for stable, safe modulation of gene expression and function. Here, we extrapolate from the current EV state of the art to a bright potential future using EVs to treat genetic diseases that are refractory to current therapeutics.

Estimating the national carbon footprint of inhalers in healthcare.

BACKGROUND: Metered dose inhalers (MDIs) contain greenhouse gases which have a disproportionate effect on the carbon footprint of healthcare. There are more environmentally friendly alternatives such as dry powder inhalers (DPIs) or soft mist inhalers (SMIs). AIMS: This study aims to approximate the carbon footprint of inhalers dispensed in Irish healthcare. METHODS: Health Market Research data was used to examine the number of inhalers sold in Ireland in 2019 via dispensing data from pharmacy IT systems. The carbon footprint per inhaler data was then used to calculate the total carbon footprint of each drug class, and an estimate for the total carbon footprint of inhalers sold in Ireland was generated. RESULTS: 4,427,287 inhalers were dispensed in Ireland in 2019 of which 2,608,433 (59%) were MDIs and 1,818,854 were DPIs/SMIs (41.1%). The total carbon equivalent of these inhalers was estimated to be 54,765 tCO2. MDIs account for 59% of inhaler units dispensed but account for 97% of inhaler-related carbon emissions. CONCLUSION: Targeting inhaler prescribing offers the potential to significantly improve the carbon footprint of Irish healthcare. Establishing the current carbon footprint of the inhalers that are prescribed, dispensed, and disposed in Ireland is a necessary baseline to inform moving towards a net zero health service.

Using the TIDieR checklist to describe the intervention of the Sedation and Weaning in Children (SANDWICH) trial.

BACKGROUND: Published reports of complex interventions in randomized controlled trials often lack sufficient detail to allow trial replication and adoption into practice. AIM: The aim of this paper is to describe our experience of using the Template for Intervention Description and Replication (TIDieR) checklist in reporting a recent trial of sedation and ventilation weaning in critically ill children (the Sedation and Weaning in Children [SANDWICH] trial). METHODS: The TIDieR 12-point checklist has been used to detail and describe the specific SANDWICH trial intervention and methods of implementation. RESULTS/DISCUSSION: Overall, we found the checklist a useful tool to direct and ensure consistency of reporting of our complex intervention used in a multi-centre clinical trial. We experienced some minor limitations in classifying training materials and delivery mode into one item because of the overlapping nature of this component. CONCLUSION: Using the TIDieR checklist to report complex interventions tested in trials provides a structured, systematic way of describing necessary detail. This allows clinicians to understand the theory behind the intervention, how it should be delivered, and the resources required. RELEVANCE TO CLINICAL PRACTICE: The SANDWICH intervention had a significant beneficial effect on reducing time on ventilation for children. The detailed description of the team-based intervention will aid replication, implementation and monitoring of fidelity in other paediatric intensive care units.

Development and initial validation of the Animal Welfare Cultural Competence Inventory (AWCCI) to assess cultural competence in animal welfare.

Cultural competence is recognized as critical to reducing disparities within human healthcare settings, but it is rarely incorporated into evaluations of companion animal services. We developed and validated an animal welfare-focused cultural competence instrument with client and provider versions. We then used the instrument to assess the relationship between animal welfare providers' cultural competence and services provided to clients in historically underserved communities. 24 providers across 17 sites participated in the provider survey. 422 clients across those sites also participated and had their service utilization data analyzed. We found a significant correlation between the number of client-provider interactions and their level of agreement within the instrument's "competence/confidence" subscale. We also found that these interactions had a significant correlation with veterinarian care and spay/neuter services. This study provides initial evidence that increasing the use of culturally competent engagement strategies has the potential to increase service utilization for pets in historically underserved communities.