Patient and specimen identification in a tertiary care pediatric hospital: Barcodes do not scan themselves.

BACKGROUND: Despite the safety improvements linked to the use of barcodes for patient and specimen identification, patient misidentification remains a leading cause of transfusion-associated reactions including fatalities. A wealth of evidence supports the use of barcodes in general, but there is less published evidence of real-world barcode compliance. This project investigates barcode scanning compliance for patient and specimen identification at a tertiary care pediatric/maternity hospital. STUDY DESIGN AND METHODS: Transfusion laboratory specimen collection noncompliance events between January 1, 2019, and December 31, 2019 were retrieved from the hospital laboratory information system. Data were analyzed including stratification of collections by collector role and collection event. A survey of blood collectors was conducted. RESULTS: Collection compliance for 6285 blood typing specimens was evaluated. Full barcode scanning identification of both patient and specimen was utilized in only 33.6% of total collections. The remaining two thirds of collections were overridden by the blood collector: no barcode scanning occurred in 31.3%, while the specimen accession label was scanned but not the patient armband in 32.3% of total collections. There were significant differences between phlebotomists and nurses, with more phlebotomists performing the full scanning and specimen scanning only, while more nurses obtained specimens without patient or specimen scanning (p < .001). Blood collectors identified hardware challenges and training gaps as key contributors to barcode noncompliance. DISCUSSION: Our study highlights an instance of poor barcode scanning compliance for patient and specimen identification. We formulated improvement strategies and launched a quality improvement project to address factors influencing noncompliance.

The Development of Clinical Self-Efficacy in Speech-Language Pathology Graduate Training: A Longitudinal Study.

PURPOSE: The study examined the development of speech-language pathology (SLP) trainee clinical self-efficacy (CSE)-defined as an individual's confidence in performing tasks related to speech and language assessment and intervention-over the course of graduate clinical training. The study also examined the relationship between preprogram experience and CSE as well as the relationship between trainee self-efficacy and clinical performance. METHOD: Participants, two cohorts of full-time SLP graduate trainees (N = 75), completed a novel SLP-specific measure of CSE at the beginning, middle, and end of a 2-year master's program and provided background information and access to practicum evaluations. RESULTS: CSE increased significantly at each point of assessment (p < .001). Students reported lower levels of self-efficacy for tasks related to evaluation compared to administration/report writing, collaboration, communication, and counseling (p < .001). Results also showed lower levels of intervention-related CSE compared to collaboration (p < .001) communication and counseling (p < .05). The variability in task-specific confidence decreased as training progressed; however, students' confidence in their evaluation skills continued to be lower relative to administration/report writing (p < .05) and collaboration (p < .01). Participants' prior clinical experience and preprogram training did not predict CSE; however, trainees with an undergraduate Communication Disorders (CD) major reported greater end-of-program self-efficacy than non-CD majors (p < .05). Trainee CSE was not found to be related to instructors' assessment of clinical performance. CONCLUSION: Findings provided preliminary insights into the nature and development of SLP-specific CSE over the course of graduate training and point to the potential pedagogical value of further examining factors associated with graduate trainee CSE in the context of clinical education.

Autism-specific parenting self-efficacy: An examination of the role of parent-reported intervention involvement, satisfaction with intervention-related training, and caregiver burden.

LAY ABSTRACT: What is already known about the topic?Parents of children with autism experience enormous challenges managing the complex needs of caring for their children. This includes coordinating multiple and complex therapies and acting as partners in treatment. Parenting self-efficacy is the confidence a person has in their ability to manage the tasks that are part of raising a child. People who have more confidence, or greater parenting self-efficacy, often feel less stressed and are more able to manage the demands of family life. This is particularly important for parents with children who have autism spectrum disorder, since they experience more parenting pressures. Although a lot is known about parenting self-efficacy in parents of neurotypical children, we do not know enough about how to help parents of children with autism spectrum disorder develop greater parenting self-efficacy.What this paper adds?This study shows that parents gain a greater sense of parenting self-efficacy when they feel more involved in their child's therapy and are more satisfied with the training they receive as part of these therapies. We also find that feeling pressure related to being a caregiver of a child with autism spectrum disorder can undermine autism-specific parenting self-efficacy. However, parents' sense of confidence was not limited by the severity of their child's symptoms.Implications for practice, research, or policyThe results suggest that there is an opportunity to help parents develop a greater sense of confidence in their ability to manage the complexities of raising a child with autism spectrum disorder by helping them feel more involved in treatment and by creating intervention-related training experiences that are more satisfying. Providers might also help by taking time to address the challenges and pressures that parents are experiencing, and helping them find ways to deal with these challenges. We suggest that there needs to be more research exploring how providers can best design interventions that support autism-specific parenting self-efficacy as a way of improving parental and child well-being.

Comparison of the Pharmacokinetics of the Phase II and Phase III Capsule Formulations of Selumetinib and the Effects of Food on Exposure: Results From Two Randomized Crossover Trials in Healthy Male Subjects.

PURPOSE: Selumetinib (AZD6244, ARRY-142886), an oral, potent, and highly selective mitogen-activated protein kinase 1/2 inhibitor with a short half-life, has shown activity across various tumor types. Before initiation of Phase III trials, the site, scale, and color (hypromellose shell from white [Phase II] to blue [Phase III]) of the selumetinib 25mg capsule manufacture was changed. We present 2 crossover trials evaluating Phase III capsules in healthy subjects. METHODS: The relative bioavailability trial was a Phase I, open-label, randomized, 3-treatment, 4-period, 6-sequence crossover trial in healthy male subjects (aged 18-55 years). Subjects received selumetinib 75mg (3 × 25 mg) Phase II or Phase III capsules, or a 35mg oral solution, during 4 dosing periods in 1 of 6 randomized treatment sequences. The food effect trial was a Phase I, open-label, randomized, 2-period crossover trial in healthy male subjects (aged 18-45 years). Subjects were randomized to 1 of 2 sequences to receive selumetinib 75mg (3 × 25 mg) Phase III capsules. In sequence 1, subjects received selumetinib after 10 hours of fasting. Following a washout period, selumetinib was administered after a high-fat meal. In sequence 2, subjects received selumetinib in the fed state, before the fasted state. Pharmacokinetic parameters were determined from serial blood sampling. FINDINGS: Twenty-seven subjects were randomized to the relative bioavailability trial; 26 completed all dosing periods. Mean selumetinib AUC was unchanged (geometric least squares mean ratio [GLSMR], 90.01% [90% CI, 81.74-99.11]). Cmax was 18% lower with the Phase III capsules (GLSMR, 81.97% [90% CI, 69.01-97.36]). A post hoc exploratory statistical analysis excluding outlying observations with later Tmax showed that Phase II and III capsules produced similar exposure in terms of Cmax and AUC. High intrasubject variability for Cmax attributed to the pharmacokinetic sampling schedule was judged to have impacted on the estimated GLSMR. In the food effect trial, 34 subjects completed both study periods. A high-fat meal reduced selumetinib Cmax compared with the fasted state (GLSMR, 49.76% [90% CI, 43.82-56.51]); AUC was minimally changed (GLSMR, 84.08% [90% CI, 80.72-87.59]). Median Tmax was prolonged by 1.49 hours. No deaths or serious adverse events were reported. IMPLICATIONS: Selumetinib 75mg (3 × 25 mg) Phase III capsules are being used in ongoing pivotal Phase III trials and should be administered in the fasted state. Based on findings from the relative bioavailability trial, pharmacokinetic sampling frequency was increased for healthy subject trials, including the food effect trial. ClinicalTrials.gov identifiers: NCT01635023 (relative bioavailability) and NCT01974349 (food effect).

The pediatric hematology/oncology educational laboratory in-training examination (PHOELIX): A formative evaluation of laboratory skills for Canadian pediatric hematology/oncology trainees.

BACKGROUND: Pediatric hematologists/oncologists need to be skilled clinicians, and must also be adept and knowledgeable in relevant areas of laboratory medicine. Canadian training programs in this subspecialty have a minimum requirement for 6 months of training in acquiring "relevant laboratory diagnostic skills." The Canadian pediatric hematology/oncology (PHO) national specialty society, C17, recognized the need for an assessment method in laboratory skills for fellows graduating from PHO training programs. PROCEDURE: Canadian pediatric hematologists/oncologists were surveyed regarding what were felt to be the essential laboratory-related knowledge and skills deemed necessary for graduating pediatric hematology/oncology trainees. The PHOELIX (Pediatric hematology/oncology educational laboratory in-training examination) was then developed to provide an annual formative evaluation of laboratory skills in Canadian PHO trainees. RESULTS: The majority of PHO respondents (89%) felt that laboratory skills are important in clinical practice. An annual formative examination including review of glass slides was implemented starting in 2010; this provides feedback regarding knowledge of laboratory medicine to both trainees and program directors (PDs). CONCLUSIONS: We have successfully created a formative examination that can be used to evaluate and educate trainees, as well as provide PDs with a tool to gauge the effectiveness of their laboratory training curriculum. Feedback has been positive from both trainees and PDs.

A transgenic zebrafish model expressing KIT-D816V recapitulates features of aggressive systemic mastocytosis.

Systemic mastocytosis (SM) is a rare myeloproliferative disease without curative therapy. Despite clinical variability, the majority of patients harbour a KIT-D816V mutation, but efforts to inhibit mutant KIT with tyrosine kinase inhibitors have been unsatisfactory, indicating a need for new preclinical approaches to identify alternative targets and novel therapies in this disease. Murine models to date have been limited and do not fully recapitulate the most aggressive forms of SM. We describe the generation of a transgenic zebrafish model expressing the human KIT-D816V mutation. Adult fish demonstrate a myeloproliferative disease phenotype, including features of aggressive SM in haematopoeitic tissues and high expression levels of endopeptidases, consistent with SM patients. Transgenic embryos demonstrate a cell-cycle phenotype with corresponding expression changes in genes associated with DNA maintenance and repair, such as reduced dnmt1. In addition, epcam was consistently downregulated in both transgenic adults and embryos. Decreased embryonic epcam expression was associated with reduced neuromast numbers, providing a robust in vivo phenotypic readout for chemical screening in KIT-D816V-induced disease. This study represents the first zebrafish model of a mast cell disease with an aggressive adult phenotype and embryonic markers that could be exploited to screen for novel agents in SM.

D-α-tocopheryl polyethylene glycol 1000 succinate: a view from FTICR MS and tandem MS.

D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) is an important polymeric excipient frequently used in drug formulation. However, differing compositions of the TPGS samples between batches are believed to result in variable performance of the formulated product. Herein, a high performance method using Fourier-transform ion cyclotron resonance (FTICR) mass spectrometry (MS) and tandem mass spectrometry (MS/MS) to analyze the composition of TPGS samples and the structure of TPGS was established. Aided by high mass accuracy and high resolution, the full MS overview of TPGS is able to provide composition information, and diagnostic fragments from collisionally activated dissociation (CAD) and electron capture dissociation (ECD) MS/MS can be used for the identification of the TPGS structure. ECD and CAD show different preferences in bond cleavage, and an interesting cross-ring cleavage was generated by CAD. Fragmentation information from ECD/ECD MS(3) is useful for providing confidence in the results. The influence of different ionization agents (Na(+), Li(+), and Ag(+)) on fragmentation of TPGS was investigated with the silver adduct providing different fragments. In addition to the methodology study, the MS and MS/MS results from four batches of TPGS samples from two manufacturers were compared. This method can be utilized for the composition and structure study of many other polymeric compounds. FTICR MS/MS demonstrated its promising role as a structural characterization tool complementary to traditional spectroscopy techniques.

Use of high resolution mass spectrometry for analysis of polymeric excipients in drug delivery formulations.

Two polymeric excipients, typically used in enabling drug delivery approaches, are Gelucire 44/14 (a product of Gattefosse s.a, St Priest, France) and polysorbate 80; these are known to improve solubility of poorly water-soluble drugs and, hence, increase their effective bioavailability. In addition to the use of Gelucire 44/14 and polysorbate 80 as excipients in drugs, they are also widely used as cosmetic and food additives. In general, complex structures and compositions of drug excipients impact performance of the formulation in vivo and consequently affect drug absorption. Therefore, a comparison between excipients from different suppliers and batches to batch would provide an indication of the impact on drug product performance and also the study of the effectiveness of the system and any problems associated with the formulation. In this study, high resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) is used to compare two different batches of Gelucire 44/14 and polysorbate 80. With the high resolving power of FTICR MS, it was possible to differentiate between batches of excipients from differences in the identified components. The improved resolution offered by FTICR MS allowed assignment of four polymeric series differences in the two batches of polysorbate 80 and the presence of one compound and three polymeric series differences in the two batches of Gelucire 44/14. The increase in the number of components assigned in the excipients batch using FTICR-MS, compared to the numbers previously assigned by lower resolution TOF MS, underlines the importance of high resolution techniques in analysis of highly complex mixtures.

Transfusion medicine problems and solutions for the pediatric hematologist/oncologist.

Blood component transfusion is an integral part of the care of children with oncologic and hematologic conditions. The complexity of transfusion medicine may however lead to challenges for pediatric hematologists/oncologists. In this review, three commonly encountered areas of transfusion medicine are explored. The approach to the investigation and management of suspected platelet refractoriness is reviewed. The unique transfusion related challenges encountered by children undergoing stem cell transplantation are also discussed. Finally, issues arising out of the care of children with hemoglobinopathies are explored, with an emphasis on the incidence of allo- and autoimmunization.

NUP98-HOXA9-transgenic zebrafish develop a myeloproliferative neoplasm and provide new insight into mechanisms of myeloid leukaemogenesis.

NUP98-HOXA9 [t(7;11) (p15;p15)] is associated with inferior prognosis in de novo and treatment-related acute myeloid leukaemia (AML) and contributes to blast crisis in chronic myeloid leukaemia (CML). We have engineered an inducible transgenic zebrafish harbouring human NUP98-HOXA9 under the zebrafish spi1(pu.1) promoter. NUP98-HOXA9 perturbed zebrafish embryonic haematopoiesis, with upregulated spi1 expression at the expense of gata1a. Markers associated with more differentiated myeloid cells, lcp1, lyz, and mpx were also elevated, but to a lesser extent than spi1, suggesting differentiation of early myeloid progenitors may be impaired by NUP98-HOXA9. Following irradiation, NUP98-HOXA9-expressing embryos showed increased numbers of cells in G2-M transition compared to controls and absence of a normal apoptotic response, which may result from an upregulation of bcl2. These data suggest NUP98-HOXA9-induced oncogenesis may result from a combination of defects in haematopoiesis and an aberrant response to DNA damage. Importantly, 23% of adult NUP98-HOXA9-transgenic fish developed a myeloproliferative neoplasm (MPN) at 19-23 months of age. In summary, we have identified an embryonic haematopoietic phenotype in a transgenic zebrafish line that subsequently develops MPN. This tool provides a unique opportunity for high-throughput in vivo chemical modifier screens to identify novel therapeutic agents in high risk AML.

Zebrafish mast cells possess an FcɛRI-like receptor and participate in innate and adaptive immune responses.

We previously identified a zebrafish mast cell (MC) lineage and now aim to determine if these cells function analogously in innate and adaptive immunity like their mammalian counterparts. Intraperitoneal (IP) injection of compound 48/80 or live Aeromonas salmonicida resulted in significant MC degranulation evident histologically and by increased plasma tryptase compared with saline-injected controls (p=0.0006, 0.005, respectively). Pre-treatment with ketotifen abrogated these responses (p=0.0004, 0.005, respectively). Cross-reactivity was observed in zebrafish to anti-human high-affinity IgE receptor gamma (FcɛRIγ) and IgE heavy chain-directed antibodies. Whole mount in situ hybridization on 7-day embryos demonstrated co-localization of cpa5, a MC-specific marker, with myd88, a toll-like receptor adaptor, and zebrafish FcɛRI subunit homologs. Zebrafish injected IP with matched dinitrophenyl-sensitized mouse (anti-DNP) IgE and DNP-BSA or trinitrophenyl-sensitized mouse (anti-TNP) IgE and TNP-BSA demonstrated increased plasma tryptase compared with mismatched controls (p=0.03, 0.010, respectively). These results confirm functional conservation and validate the zebrafish model as an in vivo screening tool for novel MC modulating agents.

Fluorescence-activated cell sorting (FACS) of whole mount in situ hybridization (WISH) labelled haematopoietic cell populations in the zebrafish.

The zebrafish is a robust animal model for studying vertebrate haematopoiesis and immune cell interactions. However, fluorescence activated cell sorting (FACS) has been limited due to a paucity of available functional zebrafish antibodies. We have developed a technique combining FACS with whole mount in situ hybridization (WISH) that enables the sorting and examining of fixed zebrafish blood cell populations at different stages of embryonic development, providing the opportunity to correlate RNA expression data with cellular morphology.

Surface-enhanced Raman scattering spectroscopy as a sensitive and selective technique for the detection of folic acid in water and human serum.

Surface-enhanced Raman scattering (SERS) is shown to give linear and sensitive concentration-dependent detection of folic acid using silver nanoparticles created via ethylene-diaminetetraacetic acid (EDTA) reduction. Optical detection by SERS overcomes the primary limitation of photodissociation encountered during the application of other shorter wavelength ultraviolet (UV)/near-UV techniques such as fluorescence based microscopy. The SERS approach in water-based samples was demonstrated and optimized using several longer wavelengths of excitation (514.5, 632.8, and 785 nm). Excitation in the green (514.5 nm) was found to achieve the best balance between photodissociation and SERS efficiency. Linear concentration dependence was observed in the range of 0.018 to 1 microM. The importance of folic acid in a clinical setting and the potential applications of this technique in a biological environment are highlighted. We demonstrate the potential to transfer this technique to real biological samples by the detection of folic acid in human serum samples by SERS.