Parenteral versus enteral fluids for infants hospitalized with bronchiolitis: The PREFER shared decision-making prospective observational study protocol.

INTRODUCTION: Incorporating shared decision-making (SDM) with children and families in hospitals was a top priority identified by patients, caregivers, and clinicians. Bronchiolitis, a common and costly reason for hospitalization in children, is an exemplar condition to study SDM in hospitals. Internationally, clinical practice guidelines differ when recommending intravenous (IV or parenteral) or nasogastric (NG or enteral) fluids for hospitalized infants with bronchiolitis who are unsafe to be fed orally. While evidence indicates that either IV or NG fluids are safe and effective, parent involvement in SDM in selecting IV or NG fluids is unknown. Our aim is to generate knowledge of SDM with parents in choosing between IV or NG fluids and the benefits and harms of these two treatment options for hospitalized children with bronchiolitis. METHOD: This is a multicenter, prospective, observational study, including children aged <12 months admitted to hospital with bronchiolitis requiring supplemental IV or NG fluids. The primary outcome will evaluate the extent of SDM in choosing IV versus NG fluids using the validated CollaboRATE tool. Secondary outcomes include the proportion of parents provided a choice of IV versus NG fluids; parent knowledge of fluid therapy; rate of fluids; length of hospital stay; and complications. DISCUSSION: This study will evaluate the extent of SDM in hospitalized infants with bronchiolitis who require IV or NG fluids and will evaluate both patient-centered and clinical outcomes that are relevant to clinical practice.

The ribosome-related protein, SBDS, is critical for normal erythropoiesis.

Although anemia is common in Shwachman- Diamond syndrome (SDS), the underlying mechanism remains unclear. We asked whether SBDS, which is mutated in most SDS patients, is critical for erythroid development. We found that SBDS expression is high early during erythroid differentiation. Inhibition of SBDS in CD34(+) hematopoietic stem cells and early progenitors (HSC/Ps) and K562 cells led to slow cell expansion during erythroid differentiation. Induction of erythroid differentiation resulted in markedly accelerated apoptosis in the knockdown cells; however, proliferation was only mildly reduced. The percentage of cells entering differentiation was not reduced. Differentiation also increased the oxidative stress in SBDS-knockdown K562 cells, and antioxidants enhanced the expansion capability of differentiating SBDS-knockdown K562 cells and colony production of SDS patient HSC/Ps. Erythroid differentiation also resulted in reduction of all ribosomal subunits and global translation. Furthermore, stimulation of global translation with leucine improved the erythroid cell expansion of SBDS-knockdown cells and colony production of SDS patient HSC/Ps. Leucine did not reduce the oxidative stress in SBDS-deficient K562 cells. These results demonstrate that SBDS is critical for normal erythropoiesis. Erythropoietic failure caused by SBDS deficiency is at least in part related to elevated ROS levels and translation insufficiency because antioxidants and leucine improved cell expansion.

Exploring the lived experience of patients and families who speak language other than English (LOE) for healthcare: developing a qualitative study.

BACKGROUND: Patients who use Languages other than English (LOE) for healthcare communication in an English-dominant region are at increased risk for experiencing adverse events and worse health outcomes in healthcare settings, including in pediatric hospitals. Despite the knowledge that individuals who speak LOE have worse health outcomes, they are often excluded from research studies on the basis of language and there is a paucity of data on ways to address these known disparities. Our work aims to address this gap by generating knowledge to improve health outcomes for children with illness and their families with LEP. BODY: We describe an approach to developing a study with individuals marginalized due to using LOE for healthcare communication, specifically using semi-structured qualitative interviews. The premise of this study is participatory research-our overall goal with this systematic inquiry is to, in collaboration with patients and families with LOE, set an agenda for creating actionable change to address the health information disparities these patients and families experience. In this paper we describe our overarching study design principles, a collaboration framework in working with different stakeholders and note important considerations for study design and execution. CONCLUSIONS: We have a significant opportunity to improve our engagement with marginalized populations. We also need to develop approaches to including patients and families with LOE in our research given the health disparities they experience. Further, understanding lived experience is critical to advancing efforts to address these well-known health disparities. Our process to develop a qualitative study protocol can serve as an example for engaging this patient population and can serve as a starting point for other groups who wish to develop similar research in this area. Providing high-quality care that meets the needs of marginalized and vulnerable populations is important to achieving an equitable, high-quality health care system. Children and families who use a Language other than English (LOE) in English dominant regions for healthcare have worse health outcomes including a significantly increased risk of experiencing adverse events, longer lengths of stay in hospital settings, and receiving more unnecessary tests and investigations. Despite this, these individuals are often excluded from research studies and the field of participatory research has yet to meaningfully involve them. This paper aims to describe an approach to conducting research with a marginalized population of children and families due to using a LOE. We detail protocol development for a qualitative study exploring the lived experiences of patients and families who use a LOE during hospitalization. We aim to share considerations when conducting research within this population of families with LOE. We highlight learning applied from the field of patient-partner and child and family-centred research and note specific considerations for those with LOE. Developing strong partnerships and adopting a common set of research principles and collaborative framework underlies our approach and initial learnings, which we hope spark additional work in this area.

De-implementing low-value continuous pulse oximetry practice in infants hospitalized with bronchiolitis: A multicentre qualitative study.

BACKGROUND: Clinical trial evidence supports the routine use of intermittent pulse oximetry in stabilized infants hospitalized with bronchiolitis. However, continuous pulse oximetry use is common. OBJECTIVE: This study aimed to understand the barriers and facilitators to de-implement continuous pulse oximetry and implement intermittent pulse oximetry in infants hospitalized with stabilized bronchiolitis. METHODS: This multicentre qualitative study interviewed attending pediatricians, residents, nurses, respiratory therapists, and caregivers of infants hospitalized with bronchiolitis at hospitals in Ontario, Canada, to explore beliefs, attitudes, and experiences regarding pulse oximetry use in bronchiolitis management. Data were analyzed using thematic analysis to understand barriers and facilitators to practice change, mapped to the Consolidated Framework for Implementation Research (CFIR) domains. RESULTS: Sixty-seven participants from six hospitals were interviewed using individual interviews and focus groups. Healthcare providers emphasized the importance of identifying and understanding who is responsible for bedside pulse oximetry practice (physicians vs. nurses). Clinical experience, knowledge of guidelines, importance versus competing priorities, and the tensions among team members due to practice variation in monitoring, influenced monitoring practice. Nurses believed in the advantages of intermittent monitoring (reduced alarm fatigue, facilitation of timely discharges, and reduced workload). Clinicians identified ways to clarify indications for continuous monitoring (based on patient risk factors), versus indications to transition to intermittent monitoring (established oral feeding, sleeping without desaturations). Caregivers did not express a clear preference for monitoring type; rather, they described the need for clear communication around interpreting monitor readings, management decisions, and care transitions. CONCLUSIONS: Understanding professional roles, clarity around local practice standards and supporting families' understanding of pulse oximetry practice is essential for practice change. These findings may inform hospital quality improvement efforts to de-implement continuous monitoring in bronchiolitis hospital care.

Enteric Fever in a Multicultural Canadian Tertiary Care Pediatric Setting: A 28-Year Review.

We undertook a 28-year review of enteric fever at a large tertiary care pediatric center. Most cases occurred in children who visited friends and relatives in the Indian subcontinent, and there was significant antibiotic resistance. Documented vaccination rates were low, and many cases also had evidence of delays in diagnosis and treatment.

Audit of demand for after-hours CT scanning services in RANZCR-accredited training departments.

INTRODUCTION: The aims of this study were to measure: (i) the growth in after-hours emergency department--referred CT (ED-CT) performed in accredited training departments between 2011 and 2013; (ii) the growth in ED CT relative to growth in ED presentations at the same hospitals; and (iii) trainee workload resulting from after-hours ED CT. METHODS: Ethics approval was obtained for all participating sites. Accredited training facilities in Australia and New Zealand with three or more trainees and serving one or more EDs were invited to participate (N = 32). Four nights were surveyed between August and December 2013. For data collection, the number of ED patients having one or more CT scans; ED CT scan total images; non-contrast head CTs; and ED patients (total and categories 1 and 2) attending the ED in the preceding 24 h and first half of calendar year were collected for 2013 and corresponding days in 2012 and 2011. Trainee staffing levels were measured. RESULTS: Eleven of 32 sites provided data for all four nights and 14 of 32 for one or more nights. A 15.7% increase in number of ED CTs between 1700 and 2200 h and 16.8% increase between 2201 and 0730 h occurred in the 2 years between 2011 and 2013 compared with a 6.9% increase in overall ED and 26% increase in categories 1 and 2 presentations over the same period. The number of CT images, however, increased 23%. CONCLUSION: Growth in demand by EDs for after-hours CT services has implications for service provision and trainee workloads in Royal Australian and New Zealand College of Radiologists-accredited training departments.

Cathepsin-L contributes to cardiac repair and remodelling post-infarction.

AIMS: Cathepsin-L (CTSL) is a member of the lysozomal cysteine protease family, which participates in remodelling of various tissues. Herein, we sought to examine the potential regulation of CTSL in cardiac remodelling post-infarction. METHODS AND RESULTS: Experimental myocardial infarction (MI) was created in CTSL-deficient (Ctsl(-/-)) mice (B6 × FSB/GnEi a/a Ctsl(fs)/J) and wild-type littermates (Ctsl(+/+)) by left coronary artery ligation. At days 3, 7, 14, and 28 post-MI, we monitored survival rate and evaluated cardiac function, morphology, and molecular endpoints of repair and remodelling. Survival was 56% in Ctsl(-/-) mice in contrast to 80% (P < 0.05) in Ctsl(+/+) mice post-MI by day 28. The Ctsl(-/-) mice exhibited greater scar dilatation, wall thinning, and worse cardiac dysfunction when compared with Ctsl(+/+) mice. Cardiac matrix metallopeptidase-9 (MMP-9) activity was also diminished, and c-kit-positive cells, natural killer cells, fibrocytes, and monocytes mobilized to peripheral blood and deposited to the infarcted myocardium were significantly decreased in Ctsl(-/-) mice. Furthermore, the local inflammatory response, and granulocyte-colony stimulating factor, stem cell factor (SCF), and stromal cell-derived factor-1 (SDF-1α) expression, as well as cell proliferation, revascularization, and myofibroblast deposition were significantly decreased in Ctsl(-/-) mice compared with Ctsl(+/+) mice. CONCLUSION: Our data indicate that CTSL regulates cardiac repair and remodelling post-MI through a mechanism with multiple pathways.

Synergistic induction of apoptosis by the Bcl-2 inhibitor ABT-737 and imatinib mesylate in gastrointestinal stromal tumor cells.

BACKGROUND: Although imatinib mesylate has revolutionized the management of patients with gastrointestinal stromal tumor (GIST), resistance and progression almost inevitably develop with long-term monotherapy. To enhance imatinib-induced cytotoxicity and overcome imatinib-resistance in GIST cells, we examined the antitumor effects of the pro-apoptotic Bcl-2/Bcl-x(L) inhibitor ABT-737, alone and in combination with imatinib. METHODS: We treated imatinib-sensitive, GIST-T1 and GIST882, and imatinib-resistant cells with ABT-737 alone and with imatinib. We determined the anti-proliferative and apoptotic effects by cell viability assay, flow cytometric apoptosis and cell cycle analysis, immunoblotting, and nuclear morphology. Synergism was determined by isobologram analysis. RESULTS: The IC(50) of single-agent ABT-737 at 72 h was 10 µM in imatinib-sensitive GIST-T1 and GIST882 cells, and 1 µM in imatinib-resistant GIST48IM cells. ABT-737 and imatinib combined synergistically in a time- and dose-dependent manner to inhibit the proliferation and induce apoptosis of all GIST cells, as evidenced by cell viability and apoptosis assays, caspase activation, PARP cleavage, and morphologic changes. Isobologram analyses revealed strongly synergistic drug interactions, with combination indices <0.5 for most ABT-737/imatinib combinations. Thus, clinically relevant in vitro concentrations of ABT-737 have single-agent antitumor activity and are synergistic in combination with imatinib. CONCLUSION: We provide the first preclinical evidence that Bcl-2/Bcl-x(L) inhibition with ABT-737 synergistically enhances imatinib-induced cytotoxicity via apoptosis, and that direct engagement of apoptotic cell death may be an effective approach to circumvent imatinib-resistance in GIST.