Daily experiences of type 1 diabetes stress across adulthood.

AIMS: Daily diabetes stressful events take a toll on individuals with type 1 diabetes, and these experiences may look different across adulthood. The aims of the current study were to understand the nature of daily diabetes stress across adulthood and explore whether these experiences differed by age. METHODS: In this qualitative study, adults with T1D (N = 199, Mage  = 46.81 years) described the most stressful event related to their diabetes each evening as part of a 14-day diary. Using a grounded theory approach, diabetes stressful events were coded for where they occurred, the source of stress (i.e. interpersonal or not), and content (e.g. sleep; blood glucose checking; frustration). RESULTS: Participants reported having a diabetes-related stressful event on 58% (M = 0.58, SD = (0.25)) of days. Daily stressful events included issues of diabetes management, diabetes-related interference to or from other areas of life, and negative impact on psychological well-being, but rarely included a social component. Older adults were less likely to report having a diabetes-related stressful event, but were more likely to report that stressful events occurred at home, compared to younger adults. CONCLUSION: The lived experience of diabetes-related stress appears similar across ages, with individuals continuing to experience generally the same types of diabetes-related events in similar frequencies. Interventions to help improve diabetes outcomes or well-being may benefit from targeting the most commonly experienced areas of stress, which includes reducing the interference of daily activities to and by diabetes management.

The separation in coordination between social- and self-regulation for emerging adults with type 1 diabetes.

To examine how self-regulation and social-regulation surrounding type 1 diabetes (T1D) management are coordinated during early emerging adulthood and whether classes of coordination relate to HbA1c and executive functioning (EF). Emerging adult participants (N = 212) with T1D (M age = 18.8 years, SD = .40) completed a 14-day diary to capture components of self-regulation and social-regulation. A mixture multi-level latent coordination model first determined the separate but coordinated factor structure of self- and social-regulation, then determined the number of distinct classes of coordination and how those classes linked to HbA1c and EF. The best-fitting model included three coordinative factors (self, mother, and father) of regulation and two distinct classes. The class with lower HbA1c and higher EF had more stable self- and social-regulation, more connections between self- and social-regulation and reflected more adaptive patterns, consistent with medical management goals. Social connection with parents may aid in regulation during this at-risk transitional time of emerging adulthood.

Pharmacological Inhibition of ERK Signaling Rescues Pathophysiology and Behavioral Phenotype Associated with 16p11.2 Chromosomal Deletion in Mice.

The human 16p11.2 microdeletion is one of the most common gene copy number variations linked to autism, but the pathophysiology associated with this chromosomal abnormality is largely unknown. The 593 kb deletion contains the ERK1 gene and other genes that converge onto the ERK/MAP kinase pathway. Perturbations in ERK signaling are linked to a group of related neurodevelopmental disorders hallmarked by intellectual disability, including autism. We report that mice harboring the 16p11.2 deletion exhibit a paradoxical elevation of ERK activity, cortical cytoarchitecture abnormalities and behavioral deficits. Importantly, we show that treatment with a novel ERK pathway inhibitor during a critical period of brain development rescues the molecular, anatomical and behavioral deficits in the 16p11.2 deletion mice. The ERK inhibitor treatment administered to adult mice ameliorates a subset of these behavioral deficits. Our findings provide evidence for potential targeted therapeutic intervention in 16p11.2 deletion carriers.SIGNIFICANCE STATEMENT The ERK/MAPK pathway is genetically linked to autism spectrum disorders and other syndromes typified by intellectual disability. We provide direct evidence connecting the ERK/MAP kinases to the developmental abnormalities in neurogenesis and cortical cytoarchitecture associated with the 16p11.2 chromosomal deletion. Most importantly, we demonstrate that treatment with a novel ERK-specific inhibitor during development rescues aberrant cortical cytoarchitecture and restores normal levels of cell-cycle regulators during cortical neurogenesis. These treatments partially reverse the behavioral deficits observed in the 16p11.2del mouse model, including hyperactivity, memory as well as olfaction, and maternal behavior. We also report a rescue of a subset of these deficits upon treatment of adult 16p11.2del mice. These data provide a strong rationale for therapeutic approaches to this disorder.

Parental Involvement and Executive Function in Emerging Adults with Type 1 Diabetes.

OBJECTIVE: To examine (a) changes in parental involvement across early emerging adulthood, (b) whether yearly fluctuations in parental involvement were associated with adherence and glycated hemoglobin (HbA1c) over time, and (c) whether higher involvement was more beneficial for those with poorer executive function (EF). METHODS: A total of 228 high school seniors (M age = 17.76) with type 1 diabetes reported on mothers' and fathers' acceptance, knowledge of diabetes activities, disclosure to mothers and fathers regarding diabetes, and adherence at four yearly time points. At baseline, participants completed performance-based measures of EF. HbA1c was collected from assay kits. RESULTS: Growth curve models revealed significant declines in disclosure to fathers and mothers' and fathers' knowledge of diabetes activities; no changes were found in mothers' or fathers' acceptance nor disclosure to mothers. Multilevel models indicated significant between-person effects for nearly all aspects of parental involvement with more acceptance, knowledge, and disclosure associated with better HbA1c and adherence. Within-person effects for disclosure to fathers, and mothers' and fathers' knowledge indicated that in years when emerging adults perceived higher amounts of these types of involvement (compared with their own average), HbA1c was lower. Within-person effects were found for acceptance to mothers, disclosure to mothers and fathers, and mothers' diabetes knowledge for adherence. Disclosure to fathers and mothers' knowledge of diabetes activities were especially beneficial for HbA1c for those with poorer EF performance. CONCLUSIONS: Parental involvement in diabetes management remains important during the high-risk time of emerging adulthood, especially for those with poorer EF.

Patient and partner illness appraisals and health among adults with type 1 diabetes.

In a study of 199 couples in which one person had type 1 diabetes, we examined how patient appraisal of the diabetes as shared versus individual was associated with collaborative, supportive and unsupportive behavior and whether patient shared illness appraisal was most beneficial for health when it occurred in the context of supportive behavior. We assessed illness appraisal among patients with type 1 diabetes and their partners and had patients complete relationship and health measures. Results showed partners were more likely than patients to hold shared illness appraisals. Patients' shared appraisals were associated with more collaborative and instrumental support, more emotional support, less protective buffering, and more overprotective behavior. When patients and partners were consistent in their shared appraisals, support was highest. Regression analysis showed collaborative and instrumental support, as well as emotional support, was related to better psychological and physical health when patients held shared compared to individual illness appraisals.

Structural model of patient-centered communication and diabetes management in early emerging adults at the transfer to adult care.

Early emerging adulthood (ages 18-25) is a time of risk for type 1 diabetes (T1D) when relationships with parents and providers are changing. We examined whether individuals' high-quality relationships with mothers are associated with greater perceptions of patient-centered communication (PCC) with their doctor and whether PCC is associated with better adherence and glycemic control through diabetes-related self-efficacy. Additionally, we tested whether associations of PCC with self-efficacy and diabetes outcomes are stronger among those who had transferred to adult care. One-year post-high school, 217 individuals with T1D (60% women, 53% in adult care) reported perceptions of maternal relationship quality, PCC, self-efficacy, and adherence. Glycemic control was measured via HbA1c assay kits. Structural equation modeling indicated good model fit and revealed indirect paths linking higher maternal relationship quality to better adherence through higher PCC, and higher PCC to better HbA1c through adherence. Transfer status moderated the link between PCC and self-efficacy, suggesting PCC may be especially important when emerging adults transfer to adult care.

Yours, Mine, and Ours: A Qualitative Analysis of the Impact of Type 1 Diabetes Management in Older Adult Married Couples.

OBJECTIVE: The purpose of this study was to understand perceptions of diabetes management responsibilities and the impact of diabetes on day-to-day activities in older adulthood for individuals with type 1 diabetes and their spouses. DESIGN AND METHODS: This qualitative content analysis used a constant-compare approach to analyze individual interviews conducted with older adults and their spouses. People with type 1 diabetes (PWD) and their spouses were interviewed regarding how they coped or dealt with diabetes, what activities they carried out or avoided because of diabetes, and how they appraised diabetes as an individual or shared problem. RESULTS: Participants (n = 52) included 26 older adults with diabetes (mean age 69 years, SD 2.56 years; 38.5% female) and their spouses (mean age 68 years, SD 5.11 years; 61.5% female). Half of the PWD (50%) and the majority of spouses (76.9%) appraised diabetes as a shared issue. Five themes emerged from the interview data: 1) Perceptions pf PWD of spouse involvement in diabetes care, 2) PWD underestimated the impact of diabetes on their spouse's daily lives, 3) gendered nature of spouses supporting diabetes management, 4) evolution of diabetes and the relationship across developmental time, and 5) differences in diabetes management among couples. CONCLUSION: Older adults with type 1 diabetes and their spouses have different perspectives regarding diabetes support and responsibility and may not always realize what support is being provided or needed to optimize effective diabetes management. Advancing age with or without diabetes complications may necessitate that spouses provide diabetes support. Diabetes management training for spouses would likely be helpful.

Self- and Social-Regulation in Type 1 Diabetes Management During Late Adolescence and Emerging Adulthood.

PURPOSE OF REVIEW: This paper aims to examine how self-regulation (i.e., cognition, emotion) and social-regulation (i.e., parents, friends, romantic partners) are interrelated risk and protective factors for type 1 diabetes management during late adolescence and emerging adulthood. RECENT FINDINGS: Problems in cognitive (e.g., executive function) and emotional (e.g., depressive symptoms) self-regulation are associated with poorer management, both at the between- and within-person levels. Better management occurs when parents are supportive and when individuals actively regulate the involvement of others (e.g., seek help, minimize interference). Friends both help and hinder self-regulation, while research on romantic partners is limited. Facets of self- and social-regulation are important risk and protective factors for diabetes management during emerging adulthood. At this time when relationships are changing, the social context of diabetes may need to be regulated to support diabetes management. Interventions targeting those with self-regulation problems and facilitating self- and social-regulation in daily life may be useful.

Host plant iridoid glycosides mediate herbivore interactions with natural enemies.

Many insect herbivores are dietary specialists capable of sequestering the secondary metabolites produced by their host plants. These defensive compounds have important but complex implications for tritrophic interactions between plants, herbivores, and natural enemies. The sequestration of host plant secondary metabolites defends herbivores from attack by generalist predators, but may also compromise the immune response, making insect herbivores more vulnerable to parasitism. Here, we investigate the role of plant secondary metabolites in mediating interactions between a specialist herbivore and its natural enemies. The host plants are two Penstemon species, Penstemon glaber and Penstemon virgatus, which are chemically defended by iridoid glycosides (IGs). First, we examined how Penstemon iridoid glycoside content influences the sequestration of IGs by a specialist herbivore, Euphydryas anicia. Then, we performed ant bioassays to assess how host plant species influences larval susceptibility to predators and phenoloxidase assays to assess the immunocompetence and potential vulnerability to parasitoids and pathogens. We found that the concentration of IGs sequestered by E. anicia larvae varied with host plant diet. Larvae reared on P. glaber sequestered more IGs than larvae reared on P. virgatus. Yet, ant predators found larvae unpalatable regardless of host plant diet and were also repelled by sugar solutions containing isolated IGs. However, E. anicia larvae reared on P. glaber showed higher levels of phenoloxidase activity than larvae reared on P. virgatus. Our results suggest that the sequestration of some secondary metabolites can effectively protect herbivores from predation, yet may also increase vulnerability to parasitism via decreased immunocompetence.

Host Plant Suitability in a Specialist Herbivore, Euphydryas anicia (Nymphalidae): Preference, Performance and Sequestration.

The checkerspot butterfly, Euphydryas anicia (Nymphalidae), specializes on plants containing iridoid glycosides and has the ability to sequester these compounds from its host plants. This study investigated larval preference, performance, and sequestration of iridoid glycosides in a population of E. anicia at Crescent Meadows, Colorado, USA. Although previous studies showed that other populations in Colorado use the host plant, Castilleja integra (Orobanchaceae), we found no evidence for E. anicia ovipositing or feeding on C. integra at Crescent Meadows. Though C. integra and another host plant, Penstemon glaber (Plantaginaceae), occur at Crescent Meadows, the primary host plant used was P. glaber. To determine why C. integra was not being used at the Crescent Meadows site, we first examined the host plant preference of naïve larvae between P. glaber and C. integra. Then we assessed the growth and survivorship of larvae reared on each plant species. Finally, we quantified the iridoid glycoside concentrations of the two plant species and diapausing caterpillars reared on each host plant. Our results showed that E. anicia larvae prefer P. glaber. Also, larvae survive and grow better when reared on P. glaber than on C. integra. Castilleja integra was found to contain two primary iridoid glycosides, macfadienoside and catalpol, and larvae reared on this plant sequestered both compounds; whereas P. glaber contained only catalpol and larvae reared on this species sequestered catalpol. Thus, although larvae are able to use C. integra in the laboratory, the drivers behind the lack of use at the Crescent Meadows site remain unclear.

Iowa Gambling Task Performance Prospectively Predicts Changes in Glycemic Control among Adolescents with Type 1 Diabetes.

OBJECTIVES: Good glycemic control is an important goal of diabetes management. Late adolescents with type 1 diabetes (T1D) are at risk for poor glycemic control as they move into young adulthood. For a subset of these patients, this dysregulation is extreme, placing them at risk for life-threatening health complications and permanent cognitive declines. The present study examined whether deficiency in emotional decision making (as measured by the Iowa Gambling Task; IGT) among teens with T1D may represent a neurocognitive risk factor for subsequent glycemic dysregulation. METHODS: As part of a larger longitudinal study, a total of 241 high-school seniors (147 females, 94 males) diagnosed with T1D underwent baseline assessment that included the IGT. Glycated hemoglobin (HbA1c), which reflects glycemic control over the course of the past 2 to 3 months, was also assessed at baseline. Of the 241,189 (127 females, 62 males, mean age=17.76, mean HbA1c=8.11) completed HbA1c measurement 1 year later. RESULTS: Baseline IGT performance in the impaired range (per norms) was associated with greater dysregulation in glycemic control 1 year later, as evidenced by an average increase in HbA1c of 2%. Those with normal IGT scores (per norms) exhibited a more moderate increase in glycemic control, with an HbA1c increase of 0.7%. Several IGT scoring approaches were compared, showing that the total scores collapsed across all trials was most sensitive to change in glycemic control. CONCLUSIONS: IGT assessment offers promise as a tool for identifying late adolescents at increased risk for glycemic dysregulation. (JINS, 2017, 23, 204-213).

The Perennial Penstemon: Variation in Defensive Chemistry Across Years, Populations, and Tissues.

Plants produce a variety of secondary metabolites that function as a defense against their natural enemies. Production of these secondary metabolites is genetically controlled, but is also phenotypically plastic and varies in response to both biotic and abiotic factors. Therefore, plant species may vary widely in their chemical defenses and such variation can be evident at temporal, spatial and tissue levels. Focusing on the chemical defenses of a native Colorado wildflower, Penstemon virgatus, we assessed the variation in iridoid glycoside (IG) content across two non-consecutive growing seasons, six natural populations and three tissue types: leaves, stems and flowers. Our results indicate that P. virgatus plants contain high concentrations of IGs (mean = 23.36% dry weight of leaves) and that IGs were differentially allocated among tissue types. Leaves contained the highest concentration of IGs, which varied quantitatively between sampling years, among plant populations, and plant parts. We also quantified leaf herbivore damage at all six populations but we found very little herbivore damage. Our study indicates that the IG concentrations of P. virgatus plants are both spatially and temporally variable. Furthermore, the high concentrations of secondary metabolites combined with the low levels of damage suggest that these plants are well defended against generalist herbivores.

The 16p11.2 deletion mouse model of autism exhibits altered cortical progenitor proliferation and brain cytoarchitecture linked to the ERK MAPK pathway.

Autism spectrum disorders are complex, highly heritable neurodevelopmental disorders affecting ∼1 in 100 children. Copy number variations of human chromosomal region 16p11.2 are genetically linked to 1% of autism-related disorders. This interval contains the MAPK3 gene, which encodes the MAP kinase, ERK1. Mutations in upstream elements regulating the ERK pathway are genetically linked to autism and other disorders of cognition including the neuro-cardio-facial cutaneous syndromes and copy number variations. We report that a murine model of human 16p11.2 deletion exhibits a reduction in brain size and perturbations in cortical cytoarchitecture. We observed enhanced progenitor proliferation and premature cell cycle exit, which are a consequence of altered levels of downstream ERK effectors cyclin D1 and p27(Kip1) during mid-neurogenesis. The increased progenitor proliferation and cell cycle withdrawal resulted in premature depletion of progenitor pools, altering the number and frequency of neurons ultimately populating cortical lamina. Specifically, we found a reduced number of upper layer pyramidal neurons and an increase in layer VI corticothalamic projection neurons, reflecting the altered cortical progenitor proliferation dynamics in these mice. Importantly, we observed a paradoxical increase in ERK signaling in mid-neurogenesis in the 16p11.2del mice, which is coincident with the development of aberrant cortical cytoarchitecture. The 16p11.2del mice exhibit anxiety-like behaviors and impaired memory. Our findings provide evidence of ERK dysregulation, developmental abnormalities in neurogenesis, and behavioral impairment associated with the 16p11.2 chromosomal deletion.

Brief report: Benefit finding and identity processes in type 1 diabetes: Prospective associations throughout adolescence.

Identity formation constitutes a core developmental task during adolescence, but may be challenged when having a chronic illness such as type 1 diabetes. The present study examined whether viewing positive benefits to one's diabetes across adolescence was related to greater identity exploration and commitment later in time. A total of 55 adolescents (10-14 years; 47% female) with type 1 diabetes participated in a six-wave study spanning 3 years (with six-month measurement intervals). Through latent growth curve modeling, Time 6 identity scores were regressed on intercept and slope terms of benefit finding through Times 1-4, simultaneously controlling for demographic and clinical variables. Identity exploration (but not commitment) at Time 6 was positively predicted by the intercept and slope of benefit finding: adolescents who find benefits in diabetes are more inclined to explore different alternatives later on in adolescence. Benefit finding may constitute a resource facilitating identity formation in adolescents with diabetes.

NF1 mutation-driven neuronal hyperexcitability sets a threshold for tumorigenesis and therapeutic targeting of murine optic glioma.

BACKGROUND: With the recognition that noncancerous cells function as critical regulators of brain tumor growth, we recently demonstrated that neurons drive low-grade glioma initiation and progression. Using mouse models of neurofibromatosis type 1 (NF1)-associated optic pathway glioma (OPG), we showed that Nf1 mutation induces neuronal hyperexcitability and midkine expression, which activates an immune axis to support tumor growth, such that high-dose lamotrigine treatment reduces Nf1-OPG proliferation. Herein, we execute a series of complementary experiments to address several key knowledge gaps relevant to future clinical translation. METHODS: We leverage a collection of Nf1-mutant mice that spontaneously develop OPGs to alter both germline and retinal neuron-specific midkine expression. Nf1-mutant mice harboring several different NF1 patient-derived germline mutations were employed to evaluate neuronal excitability and midkine expression. Two distinct Nf1-OPG preclinical mouse models were used to assess lamotrigine effects on tumor progression and growth in vivo. RESULTS: We establish that neuronal midkine is both necessary and sufficient for Nf1-OPG growth, demonstrating an obligate relationship between germline Nf1 mutation, neuronal excitability, midkine production, and Nf1-OPG proliferation. We show anti-epileptic drug (lamotrigine) specificity in suppressing neuronal midkine production. Relevant to clinical translation, lamotrigine prevents Nf1-OPG progression and suppresses the growth of existing tumors for months following drug cessation. Importantly, lamotrigine abrogates tumor growth in two Nf1-OPG strains using pediatric epilepsy clinical dosing. CONCLUSIONS: Together, these findings establish midkine and neuronal hyperexcitability as targetable drivers of Nf1-OPG growth and support the use of lamotrigine as a potential chemoprevention or chemotherapy agent for children with NF1-OPG.

Surveillance following head, neck, and chest radiotherapy: thyroid ultrasound monitoring for secondary thyroid malignancy.

Children who receive head, neck, or chest radiotherapy for various primary malignancies have increased risk for secondary thyroid malignancy. Thyroid nodules are difficult to identify by physical examination and/or laboratory tests. Thyroid ultrasound can detect non-palpable nodules without adverse side effects. We performed a retrospective chart review of 36 patients who received radiotherapy and underwent thyroid ultrasound. Forty-seven percent (n = 17) had ≥1 nodule(s) detected. Seven patients underwent thyroidectomy; four of whom were diagnosed with thyroid malignancy. Our study suggests routine use of thyroid ultrasound in high-risk patients detects subclinical thyroid nodules and potential thyroid malignancy post-radiotherapy.

Implementation of a standardised accept note to improve communication during inter-hospital transfer: a prospective cohort study.

IMPORTANCE: The transfer of patients between hospitals (interhospital transfer, IHT), exposes patients to communication errors and gaps in information exchange. OBJECTIVE: To design and implement a standardised accept note to improve communication during medical service transfers, and evaluate its impact on patient outcomes. DESIGN: Prospective interventional cohort study. SETTING: A 792-bed tertiary care hospital. PARTICIPANTS: All patient transfers from any acute care hospital to the general medicine, cardiology, oncology and intensive care unit (ICU) services between August 2020 and June 2022. INTERVENTIONS: A standardised accept note template was developed over a 9-month period with key stakeholder input and embedded in the electronic health record, completed by nurses within the hospital's Access Centre. MAIN OUTCOMES AND MEASURES: Primary outcome was clinician-reported medical errors collected via surveys of admitting clinicians within 72 hours after IHT patient admission. Secondary outcomes included clinician-reported failures in communication; presence and 'timeliness' of accept note documentation; patient length of stay (LOS) after transfer; rapid response or ICU transfer within 24 hours and in-hospital mortality. All outcomes were analysed postintervention versus preintervention, adjusting for patient demographics, diagnosis, comorbidity, illness severity, admitting service, time of year, hospital COVID census and census of admitting service and admitting team on date of admission. RESULTS: Of the 1004 and 654 IHT patients during preintervention and postintervention periods, surveys were collected on 735 (73.2%) and 462 (70.6%), respectively. Baseline characteristics were similar among patients in each time period and between survey responders and non-responders. Adjusted analyses demonstrated a 27% reduction in clinician-reported medical error rates postimplementation versus preimplementation (11.5 vs 15.8, adjusted OR (aOR) 0.73, 95% CI 0.53 to 0.99). Secondary outcomes demonstrated lower adjusted odds of clinician-reported failures in communication (aOR 0.88; 0.78 to 0.98) and rapid response/ICU transfer (aOR 0.57; 0.34 to 0.97), and improved presence (aOR 2.30; 1.75 to 3.02) and timeliness (-21.4 hours vs -8.7 hours, p<0.001) of accept note documentation. There were no significant differences in LOS or mortality. CONCLUSIONS AND RELEVANCE: Among 1658 medical patient transfers, implementing a standardised accept note was associated with improved presence and timeliness of accept note documentation, clinician-reported medical errors, failures in communication and clinical decline following transfer, suggesting that improving communication during IHT can improve patient outcomes.

Emerging Adult and Caregiver Psychosocial Experiences with Severe Hypoglycemic Events and the Perceived Impact of Nasal Glucagon: A Cross-Sectional Study.

INTRODUCTION: Severe hypoglycemic events are distressing. Although past studies have shown that young adulthood is a potentially distressing time, few studies have explored distress about severe hypoglycemia in this age group. The real-world psychosocial experiences of potential severe hypoglycemic events and the perceived impact of glucagon treatments like nasal glucagon are currently unknown. We explored perceptions of severe hypoglycemic events and impact of nasal glucagon on psychosocial experiences with these events in emerging adults with type 1 diabetes and caregivers of emerging adults and children/teens. Further, we compared perceptions of preparedness and protection in handling severe hypoglycemic events with nasal glucagon versus the emergency glucagon kit that requires reconstitution (e-kit). METHODS: This observational, cross-sectional study enrolled emerging adults (aged 18-26; N = 364) with type 1 diabetes, caregivers of emerging adults (aged 18-26; N = 138) with type 1 diabetes, and caregivers of children/teens (aged 4-17; N = 315) with type 1 diabetes. Participants completed an online survey about their experiences with severe hypoglycemia, perceptions of nasal glucagon impact on psychosocial experiences, and perceptions of feeling prepared and protected with nasal glucagon and the e-kit. RESULTS: Many emerging adults (63.7%) agreed that the experience of severe hypoglycemic events was distressing; 33.3% and 46.7% of caregivers of emerging adults and children/teens, respectively, reported distress. Participants reported positive perceptions of nasal glucagon impact, particularly improved confidence in other people's ability to help during severe hypoglycemic events: emerging adults, 81.4%; caregivers of emerging adults, 77.6%; caregivers of children/teens, 75.5%. Participants demonstrated higher perceptions of preparedness and protection for nasal glucagon than for the e-kit (p < 0.001). CONCLUSIONS: Participants reported improved confidence in other people's ability to help during severe hypoglycemic events since having nasal glucagon available. This suggests that nasal glucagon may help broaden the support network for young people with type 1 diabetes and their caregivers.

Hemophagocytic lymphohistiocytosis associated with precursor B acute lymphoblastic leukemia.

We report a case of a child with precursor-B acute lymphoblastic leukemia (ALL) who experienced refractory thrombocytopenia and massive splenomegaly during standard induction chemotherapy. He was diagnosed with hemophatocytic lymphohistiocytosis (HLH) during induction. Clinical and laboratory evaluation showed no evidence of infectious cause to HLH. Pancytopenia and HLH persisted after consolidation therapy even with remission from leukemia. After failure to control HLH with ALL-directed therapy and HLH-directed therapy, the patient underwent unrelated donor hematopoietic stem cell transplantation 8 months after diagnosis. He is 34 months post-transplant and in remission from leukemia and HLH.