Coaching for parents of children with type 1 diabetes: A randomized controlled trial.

OBJECTIVE: To assess the effectiveness of a standardized bi-weekly six-month telephone coaching intervention for parents of children with type 1 diabetes. METHODS: This single-blind randomized controlled trial followed participants for 12 months. The primary outcome was children's health-related quality of life. Secondary outcomes included treatment adherence, diabetes-related family conflict, and hemoglobin A1c. Data was collected using validated questionnaires and health records. We compared groups using a linear mixed effects model. RESULTS: 102 families were randomized (control: n = 49; intervention: n = 53). Coaching had no impact on children's overall health-related quality of life or overall secondary outcomes; however, there were patterns in subsections that suggest the possible impact of coaching. Coaching was perceived as a positive addition to routine care by 80% of families and 82% would recommend working with a coach to another family. 58% of participants would continue coaching beyond the study. CONCLUSION: Coaching did not impact overall quality of life or secondary outcomes; however, coaching was well received by families who perceived significant benefits. Patterns in subsections warrant further study. PRACTICE IMPLICATIONS: Adding a health coach into diabetes multidisciplinary care supports families in a way that is unique from their routine clinical care.

Patient Perceptions of Telehealth for Pediatric Type 1 Diabetes During the COVID-19 Pandemic: A Follow-up Study.

OBJECTIVES: There was rapid uptake of pediatric diabetes telehealth at the onset of the COVID-19 pandemic and initial studies demonstrated good usability and satisfaction. As exposure to telehealth continued to increase during the pandemic, we aimed to determine changes in telehealth usability and changes in future preferences for telehealth care. METHODS: A telehealth questionnaire was administered early in the pandemic and again more than 1 year later. Survey data were linked with a clinical data registry. A multivariable proportional odds logistic mixed-effects model was used to assess the association between exposure to telehealth and outcome of future preference for telehealth. Multivariable linear mixed-effects models were used to examine associations between exposure to early and later pandemic periods and the outcome of usability scores. RESULTS: Survey response rate was 40%, with 87 early and 168 later period participants. Virtual visits increased from 46% to 92% of all telehealth visits. Virtual visits improved in "ease of use" (p=0.0013) and "satisfaction" (p=0.045); there were no improvements in telephone visits. The odds of indicating higher preference for more future telehealth visits was 5.1-fold higher in the later pandemic group (p=0.0298). Eighty percent of participants would like their future care to include telehealth visits. CONCLUSIONS: At our tertiary diabetes centre, families' desire for future telehealth care has increased during this 1-year period of additional telehealth exposure, and virtual care has now become the preferred option. This study provides important family perspectives that can help guide development of future diabetes clinical care.

The Experience of a Gluten-free Diet in Children with Type 1 Diabetes and Celiac Disease.

OBJECTIVE: This study examined overall self-reported adherence to gluten-free diet (GFD) in children with type 1 diabetes and celiac disease (T1DCD) compared to children with celiac disease (CD). Secondary objectives included gaining insight into self-reported symptoms, barriers to adherence, and experience of a GFD between groups. METHODS: Children <18 years old who had been seen at BC Children's Hospital for T1DCD or CD were invited to participate in a web-based questionnaire and medical record review. RESULTS: A total of 26 children with T1DCD and 46 children with CD participated in the study. The groups' demographics and symptoms of CD were similar; however, a greater proportion of those with T1DCD were asymptomatic at diagnosis (T1DCD 27%; CD 7%; P = 0.016). Overall adherence to a GFD was high in both groups (T1DCD 92%; CD 100%; P = 0.38) but those with T1DCD reported a significantly less positive effect on their health (P = 0.006) and a significantly greater negative effect on activities from a GFD (P = 0.03). Children with T1DCD reported more significant barriers to eating gluten-free at home and at restaurants, specifically with social pressure, cost and taste compared to those with CD only. CONCLUSION: Children with T1DCD face specific barriers in adherence that are more impactful compared with children living with CD. These children are more often asymptomatic at diagnosis, and they go on to experience different impacts of a GFD spanning across home and social settings. Given the complexity of having a dual diagnosis, CD care should be tailored specifically to children living with T1DCD.

Usability of Virtual Visits for the Routine Clinical Care of Trans Youth during the COVID-19 Pandemic: Youth and Caregiver Perspectives.

We evaluated families' perspectives on the usability of virtual visits for routine gender care for trans youth during the COVID-19 pandemic. An online survey, which included a validated telehealth usability questionnaire, was sent to families who had a virtual Gender Clinic visit between March and August 2020. A total of 87 participants completed the survey (28 trans youth, 59 caregivers). Overall, usability was rated highly, with mean scores between "quite a bit" and "completely" in all categories (usefulness, ease of use, interface and interaction quality, reliability, and satisfaction). Caregivers reported higher usability scores compared to trans youth [mean (SD) 3.43 (0.80) vs. 3.12 (0.93), p = 0.01]. All families felt that virtual visits provided for their healthcare needs. A total of 100% of youth and caregivers described virtual appointments as safer or as safe as in-person visits. A total of 94% of participants would like virtual visits after the pandemic; families would choose a mean of two virtual and one yearly in-person visit with a multidisciplinary team. Overall, virtual gender visits for trans youth had impressive usability. Participants perceived virtual visits to be safe. For the future, a combination of virtual and in-person multidisciplinary visits is the most desired model.

Selective targeting of non-centrosomal AURKA functions through use of a targeted protein degradation tool.

Targeted protein degradation tools are becoming a new therapeutic modality, allowing small molecule ligands to be reformulated as heterobifunctional molecules (PROteolysis Targeting Chimeras, PROTACs) that recruit ubiquitin ligases to targets of interest, leading to ubiquitination and destruction of the targets. Several PROTACs against targets of clinical interest have been described, but detailed descriptions of the cell biology modulated by PROTACs are missing from the literature. Here we describe the functional characterization of a PROTAC derived from AURKA inhibitor MLN8237 (alisertib). We demonstrate efficient and specific destruction of both endogenous and overexpressed AURKA by Cereblon-directed PROTACs. At the subcellular level, we find differential targeting of AURKA on the mitotic spindle compared to centrosomes. The phenotypic consequences of PROTAC treatment are therefore distinct from those mediated by alisertib, and in mitotic cells differentially regulate centrosome- and chromatin- based microtubule spindle assembly pathways. In interphase cells PROTAC-mediated clearance of non-centrosomal AURKA modulates the cytoplasmic role played by AURKA in mitochondrial dynamics, whilst the centrosomal pool is refractory to PROTAC-mediated clearance. Our results point to differential sensitivity of subcellular pools of substrate, governed by substrate conformation or localization-dependent accessibility to PROTAC action, a phenomenon not previously described for this new class of degrader compounds.

Personal protective equipment and infection prevention and control: a national survey of UK medical students and interim foundation doctors during the COVID-19 pandemic.

BACKGROUND: The adequacy of personal protective equipment (PPE) and infection prevention and control (IPC) training in UK medical students and interim Foundation Year 1 (FiY1) doctors during the COVID-19 pandemic is unknown, as is its impact on COVID-19-related anxiety. METHODS: Cross-sectional, multi-centre study analysing self-reported adequacy of PPE and IPC training and correlation to a modified pandemic anxiety scale. Participants were current medical students and FiY1 doctors in the UK. Data were collected by an online survey. RESULTS: Participants reported that they received insufficient PPE information (43%) and IPC training (56%). Significantly, fewer participants identifying as women or BAME/mixed ethnicity reported receiving sufficient PPE information, compared with those identifying as men and White British/White Other, respectively. COVID-19-related anxiety was significantly higher in those without sufficient reported PPE or IPC training, in women compared with men, and in FiY1 doctors compared with medical students. CONCLUSIONS: With medical students currently volunteering in and imminently returning to hospitals in an educational capacity, levels of self-reported PPE and IPC training are sub-optimal. Better training is paramount to avoid harm to patients and healthcare professionals and to reduce COVID-19-related anxiety among medical students and FiY1 doctors.

Evaluation of a Province-Wide Type 1 Diabetes Care Plan for Children in the School Setting.

OBJECTIVES: The aim of this study was to identify perceptions of safety and effectiveness of a provincial type 1 diabetes school care plan, and to best inform future improvements in school care to accommodate the shifting needs of families, best clinical practices and new medical technologies. METHODS: A cross-sectional satisfaction and feedback questionnaire to inform quality improvement was offered to both families of children with type 1 diabetes who receive care at school through a Delegated Diabetes Care Plan and to their program coordinators during the 2017‒2018 school year. RESULTS: The response rate was 29.8% (160 of 537) for families and 68.2% (45 of 66) for coordinators. The majority of parents and coordinators reported that the care plan is meeting both safety and diabetes management needs. On a 7-point Likert scale, the safety score, expressed as mean (standard deviation), was 6.0 (1.2) by families and 5.7 (1.3) by coordinators, with higher scores reflecting greater satisfaction. Diabetes management was rated 5.6 (1.2) out of 7 by families, and 5.4 (0.8) out of 7 by coordinators. Families and coordinators expressed the need for individualization of care, and suggested modifications to how information is presented. There was near-unanimous support for future integration of continuous glucose-monitoring devices into the school setting. CONCLUSIONS: British Columbia's provision of diabetes care in the school setting is overall perceived to be safe and is generally well received by families and coordinators. In this study, we provide valuable information to improve the care of children with type 1 diabetes in schools, including support for further individualization of care and future integration of diabetes technology into the school setting.

Evaluation of telephone and virtual visits for routine pediatric diabetes care during the COVID-19 pandemic.

AIMS: To evaluate pediatric type 1 diabetes telehealth visits during the COVID-19 pandemic, with a focus on assessing the usability of these visits and gathering patient perspectives. METHODS: An online survey, which included a validated telehealth usability questionnaire, was offered via email to families with a telephone or virtual visit since the COVID-19-related cancellation of routine in-person care. Survey data was linked with the British Columbia (BC) Clinical Diabetes Registry. Outcomes between groups were assessed using Welch's t-test. Associations with type of visit as well as with desire to return to in-person care were assessed with logistic regression models. RESULTS: The response rate was 47%. Of 141 survey respondents, 87 had clinical data available in the BC Clinical Diabetes Registry, and thus were included in our analysis. Overall, telephone and virtual visits were rated highly for usability. Telephone visits were easier to learn to use, and simpler to understand; however, telephone and virtual visits were similar across multiple areas. No factors associated with choosing one type of visit over the other, or with desire to return to in-person care, could be identified. 72% of participants want future telehealth care; however, some would like all future care to be in-person. CONCLUSIONS: Telephone and virtual visits had impressive usability. Many families want telehealth to play a significant part in their future care.

Biodistribution and Dosimetry of Intraventricularly Administered 124I-Omburtamab in Patients with Metastatic Leptomeningeal Tumors.

Radiation dose estimations are key for optimizing therapies. We studied the role of 124I-omburtamab (8H9) given intraventricularly in assessing the distribution and radiation doses before 131I-omburtamab therapy in patients with metastatic leptomeningeal disease and compared it with the estimates from cerebrospinal fluid (CSF) sampling. Methods: Patients with histologically proven malignancy and metastatic disease to the central nervous system or leptomeninges who met eligibility criteria for 131I-omburtamab therapy underwent immuno-PET imaging with 124I-8H9 followed by 131I-8H9 antibody therapy. Patients were imaged with approximately 74 MBq of intraventricular 124I-omburtamab via an Ommaya reservoir. Whole-body PET images were acquired at approximately 4, 24, and 48 h after administration and analyzed for dosimetry calculations. Peripheral blood and CSF samples were obtained at multiple time points for dosimetry estimation. Results: Forty-two patients with complete dosimetry and therapy data were analyzed. 124I-omburtamab PET-based radiation dosimetry estimations revealed mean (±SD) absorbed dose to the CSF for 131I-8H9 of 0.62 ± 0.40 cGy/MBq, compared with 2.22 ± 2.19 cGy/MBq based on 124I-omburtamab CSF samples and 1.53 ± 1.37 cGy/MBq based on 131I-omburtamab CSF samples. The mean absorbed dose to the blood was 0.051 ± 0.11 cGy/MBq for 124I-omburtamab samples and 0.07 ± 0.04 cGy/MBq for 131I-omburtamab samples. The effective whole-body radiation dose for 124I-omburtamab was 0.49 ± 0.27 mSv/MBq. The mean whole-body clearance half-time was 44.98 ± 16.29 h. Conclusion: PET imaging with 124I-omburtamab antibody administered intraventricularly allows for noninvasive estimation of dose to CSF and normal organs. High CSF-to-blood absorbed-dose ratios are noted, allowing for an improved therapeutic index to leptomeningeal disease and reduced systemic doses. PET imaging-based estimates were less variable and more reliable than CSF sample-based dosimetry.

A Phase I/II Study for Analytic Validation of 89Zr-J591 ImmunoPET as a Molecular Imaging Agent for Metastatic Prostate Cancer.

PURPOSE: Standard imaging for assessing osseous metastases in advanced prostate cancer remains focused on altered bone metabolism and is inadequate for diagnostic, prognostic, or predictive purposes. We performed a first-in-human phase I/II study of (89)Zr-DFO-huJ591 ((89)Zr-J591) PET/CT immunoscintigraphy to assess performance characteristics for detecting metastases compared with conventional imaging modalities (CIM) and pathology. EXPERIMENTAL DESIGN: Fifty patients with progressive metastatic castration-resistant prostate cancers were injected with 5 mCi of (89)Zr-J591. Whole-body PET/CT scans were obtained, and images were analyzed for tumor visualization. Comparison was made to contemporaneously obtained bone scintigraphy and cross-sectional imaging on a lesion-by-lesion basis and with biopsies of metastatic sites. RESULTS: Median standardized uptake value for (89)Zr-J591-positive bone lesions (n = 491) was 8.9 and for soft-tissue lesions (n = 90), it was 4.8 (P < 0.00003). (89)Zr-J591 detected 491 osseous sites compared with 339 by MDP and 90 soft-tissue lesions compared with 124 by computed tomography (CT). Compared with all CIMs combined, (89)Zr-J591 detected an additional 99 osseous sites. Forty-six lesions (21 bone and 25 soft tissue) were biopsied in 34 patients; 18 of 19 (89)Zr-J591-positive osseous sites and 14 of 16 (89)Zr-J591-positive soft tissue sites were positive for prostate cancer. The overall accuracy of (89)Zr-J591 was 95.2% (20 of 21) for osseous lesions and 60% (15 of 25) for soft-tissue lesions. CONCLUSIONS: (89)Zr-J591 imaging demonstrated superior targeting of bone lesions relative to CIMs. Targeting soft-tissue lesions was less optimal, although (89)Zr-J591 had similar accuracy as individual CIMs. This study will provide benchmark data for comparing performance of proposed prostate-specific membrane antigen (PSMA) targeting agents for prostate cancer.