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People with diabetes taking insulin are at risk of severe hypoglycemia, an unpredictable, life-threatening event that requires assistance from others. Outside the clinical setting, glucagon is indicated for the treatment of hypoglycemia. However, there is significant unmet medical need to improve successful administration of glucagon by caregivers and acquaintances. This study assesses perceptions about glucagon delivery and potential effects of 2 glucagon delivery devices for severe hypoglycemia. Qualitative interviews were conducted with people with diabetes (patients), caregivers, and acquaintances from a general population panel composed of individuals across the United States who have agreed to be recruited for research studies. Participants were recruited via email with a link to an online screener to determine eligibility. Experienced qualitative researchers conducted telephone interviews after a semistructured discussion guide, developed by the authors, that focused on aspirational device features and perceptions about the 2 devices: nasal glucagon and autoinjector glucagon; visuals of the instructions for use were displayed. Verbatim transcripts were developed, and a qualitative analysis software program, MaxQDA, was used to code responses and themes that emerged from the data. A total of 45 (15 patients, 15 caregivers, and 15 acquaintances) interviews were conducted (mean ages, 55, 40, and 51, respectively). The most frequently spontaneously identified aspirational features for a new glucagon device were ease of use (29 [64%]), including being uncomplicated, premixed/ready to use, and ability to use quickly; small/easy to carry (9 [20%]); needle-free/no long needles (8 [18%]); and easy instructions (4 [9%]). In general, participants indicated that having a glucagon delivery device on hand would make them feel prepared, protected, and confident that others could assist in the event of severe hypoglycemia. More participants across all subgroups preferred nasal glucagon versus autoinjector glucagon (33 [73%] vs 12 [27%]). Favorable comments about nasal glucagon included that it appeared to be easy to carry, easy to use, and lacked a needle, that one does not need to remove clothing to use it, and that others likely would be more comfortable using it. Favorable comments about autoinjector glucagon included that it was familiar as a rescue device and that patients felt confident that the full dose would be delivered with it. There may be more hesitation using autoinjector glucagon versus nasal glucagon because of anxiety about needles and locating an injection site. Participants indicated that they would feel more comfortable socially using nasal glucagon because it was viewed as more discreet and less embarrassing than using autoinjector glucagon; it was also considered less traumatic for use in children. This research suggests that patients with diabetes, caregivers, and acquaintances prefer a device that is simple, compact, and ready to use. Nasal glucagon was generally preferred over autoinjector glucagon primarily because it lacks a needle and it appears to be less complicated.

Background: For individuals managing diabetes, the administration of glucagon for severe hypoglycemia can be lifesaving, yet, until recently, there were no easy-to-use devices for these stressful emergencies. New products have emerged to meet this need, including nasal glucagon (NG) and auto-injector glucagon (AI). This study evaluated the psychometric properties of a new measure, the Glucagon Device Attitudes Questionnaire (GDAQ), in assessing attitudes toward NG and AI from the perspectives of persons with diabetes on insulin (PWDs), caregivers, and acquaintances. Methods: Developed based on qualitative research, the GDAQ consists of 38 rating items for each device and 16 direct-elicitation of attitudes of device relative to each other. It was administered to participants via a cross-sectional online survey. Twenty-six rating items were included in principal component analysis and confirmatory factor analysis. Items comprising each factor were averaged to form scales. Additionally, 12 direct elicitation items were averaged to form an overall \"Attitudes\" scale. Reliability and validity analyses were conducted. Descriptive statistics were provided for the rating items not included in the factor analysis. Results: A total of 405 PWDs, 313 caregivers, and 305 acquaintances participated. Three factors were identified: \"Prepared and Protected\" (7 items), \"Hesitation\" (12 items), and \"Device Perceptions by Others\" (7 items); factor loadings ranged from 0.13 to 0.92, 0.50 to 0.89, and 0.16 to 0.92, respectively. Cronbach's alpha for the four scales ranged from 0.76 to 0.96. Correlations of the scales with their global item ranged from 0.30 to 0.90. The items outside of the factor analysis showed good distribution in responses and differentiation between the two devices. Discussion: This study supports the validity and reliability of the GDAQ, which successfully conceptualizes attitudes towards devices for administering glucagon among different respondent groups. Use of the GDAQ can help guide the development and testing of new glucagon drug/device combinations. Keywords: diabetes, severe hypoglycemic events, glucagon delivery device, patient attitudes

In a randomized trial, once-weekly insulin efsitora, administered in a fixed-dose regimen, was noninferior to once-daily glargine in reducing hemoglobin levels in patients with type 2 diabetes who had not previously received insulin.

Abstract Context Safety concerns have been raised regarding premature mortality, diabetes, neoplasia, and cerebrovascular disease in association with GH therapy. Objective To assess incidence of key safety outcomes. Design Prospective, multinational, observational study (1999 to 2015). Setting A total of 22,311 GH-treated children from 827 investigative sites in 30 countries. Patients Children with growth disorders. Interventions GH treatment. Main outcome measures Standardized mortality ratio (SMR) and standardized incidence ratio (SIR) with 95% CIs for mortality, diabetes, and primary cancer using general population registries. Results Predominant short stature diagnoses were GH deficiency (63%), idiopathic short stature (13%), and Turner syndrome (8%), with mean ± SD follow-up of 4.2 ± 3.2 years (∼92,000 person-years [PY]). Forty-two deaths occurred in patients with follow-up, with an SMR (95% CI) of 0.61 (0.44, 0.82); the SMR was elevated for patients with cancer-related organic GH deficiency [5.87 (3.21, 9.85)]. Based on 18 cases, type 2 diabetes mellitus (T2DM) risk was elevated [SIR: 3.77 (2.24, 5.96)], but 72% had risk factors. In patients without cancer history, 14 primary cancers were observed [SIR: 0.71 (0.39, 1.20)]. Second neoplasms occurred in 31 of 622 cancer survivors [5.0%; 10.7 (7.5, 15.2) cases/1000 PY] and intracranial tumor recurrences in 67 of 823 tumor survivors [8.1%; 16.9 (13.3, 21.5) cases/1000 PY]. All three hemorrhagic stroke cases had risk factors. Conclusions GeNeSIS (Genetics and Neuroendocrinology of Short Stature International Study) data support the favorable safety profile of pediatric GH treatment. Overall risk of death or primary cancer was not elevated in GH-treated children, and no hemorrhagic strokes occurred in patients without risk factors. T2DM incidence was elevated compared with the general population, but most cases had diabetes risk factors. Safety of GH therapy was assessed in a pediatric observational study. Death and primary cancer rates were not higher than in the general population; T2DM rate was higher owing to risk factors.

Aims/hypothesis Valid and reliable patient-reported outcome measures are vital for assessing disease impact, responsiveness to healthcare and the cost-effectiveness of interventions. A recent review has questioned the ability of existing measures to assess hypoglycaemia-related impacts on health-related quality of life for people with diabetes. This mixed-methods project was designed to produce a novel health-related quality of life patient-reported outcome measure in hypoglycaemia: the Hypo-RESOLVE QoL. Methods Three studies were conducted with people with diabetes who experience hypoglycaemia. In Stage 1, a comprehensive health-related quality of life framework for hypoglycaemia was elicited from semi-structured interviews ( N =31). In Stage 2, the content validity and acceptability of draft measure content were tested via three waves of cognitive debriefing interviews ( N =70 people with diabetes; N =14 clinicians). In Stage 3, revised measure content was administered alongside existing generic and diabetes-related measures in a large cross-sectional observational survey to assess psychometric performance ( N =1246). The final measure was developed using multiple evidence sources, incorporating stakeholder engagement. Results A novel conceptual model of hypoglycaemia-related health-related quality of life was generated, featuring 19 themes, organised by physical, social and psychological aspects. From a draft version of 76 items, a final 14-item measure was produced with satisfactory structural (χ 2 =472.27, df =74, p <0.001; comparative fit index =0.943; root mean square error of approximation =0.069) and convergent validity with related constructs ( r =0.46–0.59), internal consistency (α=0.91) and test–retest reliability (intraclass correlation coefficient =0.87). Conclusions/interpretation The Hypo-RESOLVE QoL is a rigorously developed patient-reported outcome measure assessing the health-related quality of life impacts of hypoglycaemia. The Hypo-RESOLVE QoL has demonstrable validity and reliability and has value for use in clinical decision-making and as a clinical trial endpoint. Data availability All data generated or analysed during this study are included in the published article and its online supplementary files ( https://doi.org/10.15131/shef.data.23295284.v2 ). Graphical Abstract

A severe hypoglycemia (SH) episode is an acute, high-stress moment for the caregivers of persons with diabetes (PWD). We compared the success rates of nasal glucagon (NG) and injectable glucagon (IG) administration for PWD-trained and untrained users in treating simulated SH episodes. Thirty-two PWD-trained users and 33 untrained users administered NG and IG to high-fidelity manikins simulating treatment of an SH emergency. Simulation rooms resembled common locations with typical diabetic supplies and stressor elements mimicking real-life SH environments. Success rate and time to administer glucagon were measured. Of all the PWD-trained and untrained users, 58/64 (90.6%) could successfully deliver NG, while 5/63 (7.9%) could successfully deliver IG. For NG simulations, 28/31 (90.3%) PWD-trained users and 30/33 (90.9%) untrained users could successfully administer the dose (mean time 47.3 seconds and 44.5 seconds, respectively). For IG simulations, 5/32 (15.6%) PWD-trained users successfully injected IG (mean time 81.8 seconds), whereas none (0/31 [0%]) of the untrained users were successful. Reasons for unsuccessful administration of NG included oral administration and incomplete pushing of the device plunger. For IG, inability to perform reconstitution steps, partial dose delivery, and injection at an inappropriate site were the causes for failure. With or without training, the success rate for administering NG was 90.6%, whereas it was only 7.9% for IG. NG was easily and quickly administered even by untrained users, whereas training was necessary for successful administration of IG. NG may expand the community of caregivers who can help PWD during an SH episode. = injectable glucagon; = nasal glucagon; = person with diabetes; = severe hypoglycemia; = type 1 diabetes; = type 2 diabetes.

CONTEXT:Although pediatric growth hormone (GH) treatment is generally considered safe for approved indications, concerns have been raised regarding potential for increased risk of mortality in adults treated with GH during childhood. OBJECTIVE:To assess mortality in children receiving GH. DESIGN:Prospective, multinational, observational study. SETTING:Eight hundred twenty-seven study sites in 30 countries. PATIENTS:Children with growth disorders. INTERVENTIONS:GH treatment during childhood. MAIN OUTCOME MEASURE:Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) using age- and sex-specific rates from the general population. RESULTS:Among 9504 GH-treated patients followed for ≥4 years (67,163 person-years of follow-up), 42 deaths were reported (SMR, 0.77; 95% CI, 0.56 to 1.05). SMR was significantly elevated in patients with history of malignant neoplasia (6.97; 95% CI, 3.81 to 11.69) and borderline elevated for those with other serious non-GH-deficient conditions (2.47; 95% CI, 0.99-5.09). SMRs were not elevated for children with history of benign neoplasia (1.44; 95% CI, 0.17 to 5.20), idiopathic GHD (0.11; 95% CI, 0.02 to 0.33), idiopathic short stature (0.20; 95% CI, 0.01 to 1.10), short stature associated with small for gestational age (SGA) birth (0.66; 95% CI, 0.08 to 2.37), Turner syndrome (0.51; 95% CI, 0.06 to 1.83), or short stature homeobox-containing (SHOX) gene deficiency (0.83; 95% CI, 0.02 to 4.65). CONCLUSIONS:No significant increases in mortality were observed for GH-treated children with idiopathic GHD, idiopathic short stature, born SGA, Turner syndrome, SHOX deficiency, or history of benign neoplasia. Mortality was elevated for children with prior malignancy and those with underlying serious non-GH-deficient medical conditions.

A survey was conducted in eight countries to examine conversations around, and experiences and treatments during, severe hypoglycemia among people with diabetes and caregivers of people with diabetes. This article reports a subgroup analysis from the United States involving 219 people with diabetes and 210 caregivers. Most respondents (79.7%) did not use professional health care services during their most recent severe hypoglycemic event, and 40.3% did not report the event to their health care providers at a subsequent follow-up visit. Hypoglycemic events left respondents feeling scared (70.9%), unprepared (42.7%), and helpless (46.9%). These clinically important psychosocial impacts on people with diabetes and caregivers underscore the need for conversations about hypoglycemia prevention and management.

Background/Aims: Magnetic resonance imaging (MRI) is used to investigate the etiology of growth hormone deficiency (GHD). This study examined relationships between MRI findings and clinical/hormonal phenotypes in children with GHD in the observational Genetics and Neuroendocrinology of Short Stature International Study, GeNeSIS. Methods: Clinical presentation, hormonal status and first-year GH response were compared between patients with pituitary imaging abnormalities (n = 1,071), patients with mutations in genes involved in pituitary development/GH secretion (n = 120) and patients with idiopathic GHD (n = 7,039). Results: Patients with hypothalamic-pituitary abnormalities had more severe phenotypes than patients with idiopathic GHD. Additional hormonal deficiencies were found in 35% of patients with structural abnormalities (thyroid-stimulating hormone > adrenocorticotropic hormone > luteinizing hormone/follicle-stimulating hormone > antidiuretic hormone), most frequently in patients with septo-optic dysplasia (SOD). Patients with the triad [ectopic posterior pituitary (EPP), pituitary aplasia/hypoplasia and stalk defects] had a more severe phenotype and better response to GH treatment than patients with isolated abnormalities. The sex ratio was approximately equal for patients with SOD, but there was a significantly higher proportion of males (approximately 70%) in the EPP, pituitary hypoplasia, stalk defects, and triad categories. Conclusion: This large, international database demonstrates the value of classification of GH-deficient patients by the presence and type of hypothalamic-pituitary imaging abnormalities. This information may assist family counseling and patient management.

Background/Aims: The short stature homeobox-containing (SHOX) gene is one of many genes that regulate longitudinal growth. The SHOX deficiency (SHOX-D) phenotype, caused by intragenic or regulatory region defects, ranges from normal stature to mesomelic skeletal dysplasia. We investigated differences in radiological anomalies between patients with SHOX-D and Turner syndrome (TS) and the effect of 2 years of growth hormone (GH) treatment on these anomalies. Methods: Left hand/wrist, forearm and lower leg radiographs were assessed at baseline and after 2 years in children with genetically confirmed SHOX-D (GH-treated and untreated groups) and TS (GH-treated) in a randomised, controlled, multinational study. Results: Radiological anomalies of hand, wrist and forearm were common in SHOX-D and TS. Radial bowing appeared more prevalent in SHOX-D, while lower leg anomalies were more common in TS. There were no significant differences in radiological findings between GH-treated and untreated patients with SHOX-D after 2 years. Conclusion: GH treatment had no systematic effect on skeletal findings in SHOX-D, based on limited radiological differences between the GH-treated and untreated groups at 2 years. Bone age radiographs allow assessment of radiological signs indicating a potential diagnosis of SHOX-D and may lead to earlier genetic confirmation and initiation of GH therapy.