A Comparative Study of Dasiglucagon Ready-to-Use Autoinjector and Glucagon Emergency Kit During Rescue from Simulated Severe Hypoglycemia.

Background: Severe hypoglycemic episodes are life-threatening events demanding rapid administration of glucagon by a caregiver or bystander. The glucagon analog dasiglucagon is stable in aqueous formulation and therefore suitable for delivery in a ready-to-use autoinjector, potentially increasing speed and ease of use compared with standard glucagon emergency kits (GEKs). Methods: In an open label, randomized, crossover, comparative device handling study, trained caregivers and untrained bystanders administered the dasiglucagon autoinjector or Eli Lilly GEK to manikins in a simulated emergency hypoglycemia situation. Results: In total, 54 participants were randomized (18 patient-caregiver pairs and 18 bystanders). Overall, 94% of trained caregivers were able to administer the dasiglucagon autoinjector successfully within 15 min, compared with 56% for the GEK (P < 0.05). A greater proportion of trained caregivers and untrained bystanders successfully prepared and administered the dasiglucagon autoinjector within 2 min compared with the GEK (P < 0.005 and P < 0.05, respectively). Time to successful completion was also significantly faster with the dasiglucagon autoinjector than with the GEK (P < 0.005 for both groups). Most study participants preferred the dasiglucagon autoinjector over the GEK (94%, P < 0.001) and rated it as easier (90%, P < 0.001) and less stressful to use (94%, P < 0.001) than the GEK. Conclusion: Dasiglucagon autoinjector was more rapidly and reliably administered, and users reported greater ease of use and usage satisfaction than with the GEK. Thus, dasiglucagon autoinjector has the potential to improve speed and ease of treatment in severe hypoglycemic events, providing a better usage experience for rescuing individuals and enabling faster recovery for patients.

"It's embarrassing. I get angry. I get frustrated.": Understanding severe hypoglycemia and glucagon usage from the perspectives of people with type 1 diabetes.

Introduction: This study characterized the emotional impact of severe hypoglycemia, views of glucagon, and barriers to glucagon use from the perspective of adults with type 1 diabetes (T1D). Methods: Participants included individuals recruited from the T1D Exchange online community. The current study conducted 7 focus groups consisting of adults with T1D (N = 38, average age 49.4, SD = 16.11 years). Average duration of diabetes was 34.4 years (SD = 17.3) and average self-reported A1c was 6.8 % (SD = 0.7). Focus group interviews were recorded, transcribed, and thematically analyzed. Results: A range of emotions was expressed about severe hypoglycemia including fear, anxiety, stress, frustration, shame, and embarrassment. Participants frequently identified prescription cost and insurance deductibles as barriers to glucagon use. Participants were also concerned about ease of administration-how difficult it is to prepare the glucagon in an emergency. Many participants expressed a preference for auto-injectables over nasal administration. Timing of glucagon action and time to recovery were high priorities. Some participants, while they had not self-administered glucagon, were interested in a mini-dose glucagon they could self-administer. They also identified desirable characteristics of glucagon treatment including reduced cost, long shelf-life, and quick activation. Conclusions: These results highlight the attitudes about severe hypoglycemia and emergency treatment with glucagon. Healthcare professionals should assess glucagon training needs and knowledge when they meet with their patients with diabetes.

Recombinant activated factor VII safety in trauma patients: results from the CONTROL trial.

BACKGROUND: Safety data on recombinant activated factor VII (rFVIIa, NovoSeven; Novo Nordisk A/S, Bagsværd, Denmark) in actively hemorrhaging trauma patients are limited. We present detailed safety data from a large multicenter, randomized, placebo-controlled phase III study (the CONTROL trial). METHODS: Data from 560 patients were analyzed. Subjects were monitored for adverse events (AEs) after rFVIIa or placebo administration. Incidences, timing, and presence of risk factors were reported by site investigators, supported by external study monitors and overseen by an independent Data Monitoring Committee. RESULTS: There were no differences in overall mortality, organ system failure, or AEs, serious AEs, or medical events of special interest. Arterial and venous thromboembolic (TE) events and their risk factors were similar in both groups. The greatest risk factor for TE events was a chest injury requiring mechanical ventilation >3 days (86%). There were four site investigator-reported myocardial infarctions in the rFVIIa group of which only one met diagnostic criteria preestablished by the Data Monitoring Committee. There were no reported myocardial infarctions in the placebo group. Troponins were increased in 30% of all patients. The rate of acute respiratory distress syndrome was lower in the rFVIIa (3.0%) than in the placebo (7.2%) group (p = 0.022). CONCLUSIONS: This represents the largest placebo-controlled dataset of rFVIIa use in trauma patients to date. In this prospective study of critically bleeding trauma patients, rFVIIa use was associated with an imbalance of investigator-reported Acute myocardial infarction/non-ST segment elevation myocardial infarction (AMI/NSTEMI), but was not associated with an increased risk for other AEs, including TE complications.

Results of the CONTROL trial: efficacy and safety of recombinant activated Factor VII in the management of refractory traumatic hemorrhage.

BACKGROUND: Traumatic coagulopathy contributes to early death by exsanguination and late death in multiple organ failure. Recombinant Factor VIIa (rFVIIa, NovoSeven) is a procoagulant that might limit bleeding and improve trauma outcomes. METHODS: We performed a phase 3 randomized clinical trial evaluating efficacy and safety of rFVIIa as an adjunct to direct hemostasis in major trauma. We studied 573 patients (481 blunt and 92 penetrating) who bled 4 to 8 red blood cell (RBC) units within 12 hours of injury and were still bleeding despite strict damage control resuscitation and operative management. Patients were assigned to rFVIIa (200 µg/kg initially; 100 µg/kg at 1 hour and 3 hours) or placebo. Intensive care unit management was standardized using evidence-based trauma "bundles" with formal oversight of compliance. Primary outcome was 30-day mortality. Predefined secondary outcomes included blood products used. Safety was assessed through 90 days. Study powering was based on prior randomized controlled trials and large trauma center databases. RESULTS: Enrollment was terminated at 573 of 1502 planned patients because of unexpected low mortality prompted by futility analysis (10.8% vs. 27.5% planned/predicted) and difficulties consenting and enrolling sicker patients. Mortality was 11.0% (rFVIIa) versus 10.7% (placebo) (p = 0.93, blunt) and 18.2% (rFVIIa) versus 13.2% (placebo) (p = 0.40, penetrating). Blunt trauma rFVIIa patients received (mean ± SD) 7.8 ± 10.6 RBC units and 19.0 ± 27.1 total allogeneic units through 48 hours, and placebo patients received 9.1 ± 11.3 RBC units (p = 0.04) and 23.5 ± 28.0 total allogeneic units (p = 0.04). Thrombotic adverse events were similar across study cohorts. CONCLUSIONS: rFVIIa reduced blood product use but did not affect mortality compared with placebo. Modern evidence-based trauma lowers mortality, paradoxically making outcomes studies increasingly difficult.

The prognosis of impaired left ventricular systolic function and heart failure in a middle-aged and elderly population in an urban population segment of Copenhagen.

AIMS: To determine the prognosis, total mortality and cardiac morbidity, of patients with left ventricular systolic dysfunction and heart failure (HF) in a general population sample. METHODS AND RESULTS: A total of 764 subjects, 432 females and 332 males, median age (range) 66 years (50-89), participated in this cross sectional survey. The study population was recruited from randomly selected general practitioners and stratified to include a minimum of 150 persons in each age decade stratum. Each participant filled in a heart failure questionnaire and ECG, blood tests and echocardiography were performed. Median (range) follow-up was 1145 (51-1197) days. Subjects with LVEF < or = 0.40 had a significantly higher all-cause mortality (27.8% vs. 5.6%, P<0.0001), admission rate for HF (25.0% vs. 1.9%, P<0.0001) and for other cardiac causes (25.0% vs. 6.3%, P<0.0001) than in subjects with LVEF>0.40. The age and gender adjusted 2-year relative risk of death was 4.6 (95% C.I.=1.6-13.2). No significant difference in mortality was found between subjects with or without heart failure symptoms. CONCLUSION: Significantly higher mortality as well as cardiac morbidity was found in subjects with symptomatic and asymptomatic LV systolic dysfunction compared to those with normal systolic function. These conditions were among the strongest predictors of all-cause mortality and cardiac morbidity.