An Analysis of Driving Performance Measures Used to Assess the Effects of Medications on Drowsiness, Sedation and Driving Impairment

The objective of this paper was to discuss driving scenarios and associated driving performance measures on their ability to demonstrate drowsiness, sedation, and driving impairment. The basis of this paper was a study that utilized a randomized, double-blind, double-dummy, four-treatment, four-period crossover trial in the Iowa Driving Simulator (IDS). Participants were 40 licensed drivers with seasonal allergic rhinitis who were 25 to 44 years of age. Treatments were Fexofenadine, diphenhydramine, alcohol, or placebo, given at weekly intervals before participants drove for 1 hour in the IDS. Measures examined included coherence, amplitude, phase angle, RMS error, following distance and behavior, lane keeping, response to unexpected vehicle intrusion and drowsiness. Study results show that sedating antihistamines impair driving performance as seriously as alcohol. Statistically significant but small correlations were found between subjective drowsiness and minimum following distance, steering instability, and left-lane excursions but no correlation was greater than 0.21. Drowsiness was a weak predictor of driving impairment. This paper discusses these and other finding with an emphasis on the adequacy of driving scenarios and the sensitivity of driving performance measures analyzed

Consistency of Quantitative Scores of Hypoglycemia Severity and Glycemic Lability and Comparison with Continuous Glucose Monitoring System Measures in Long-Standing Type 1 Diabetes

Background: In long-standing type 1 diabetes (T1D), loss of endogenous insulin secretion and glucose dysregulation can lead to severe hypoglycemia and associated complications. Here, we report the serial consistency and the correlation between different scores that characterize glucose dysregulation using self-monitoring of blood glucose (SMBG), in a cohort of T1D individuals being evaluated for transplant eligibility in Clinical Islet Transplantation Consortium trials. Subjects and Methods: In total, 152 C-peptide–negative T1D subjects with at least one severe hypoglycemia episode in the prior year documented SMBG at enrollment and every 6 months until deemed ineligible or transplanted. SMBG was used to calculate the HYPO score, Lability Index (LI), and mean amplitude of glycemic excursion (MAGE). Additionally, a blinded continuous glucose monitoring system (CGMS) was worn for 72 h at enrollment and every 12 months. Results: In this cohort, LI was the most consistent (intraclass correlation coefficient=0.70) over time, followed by the HYPO score (0.51), with MAGE being the least consistent (0.36). Although MAGE and LI were highly correlated with each other, neither correlated with CGMS SD or glucose coefficient of variation (CV). Subjects spent a median of 97 min/day at <54 mg/dL using CGMS. The HYPO score correlated with CGMS time below 54 mg/dL and glucose CV. Conclusions: The HYPO score and LI are more consistent than MAGE in patients with established T1D experiencing severe hypoglycemic events and may be especially useful both for identifying subjects experiencing the greatest difficulty in maintaining glycemic control and for longitudinal assessment of novel interventions

Long-term Outcomes With Islet-Alone and Islet-After-Kidney Transplantation for Type 1 Diabetes in the Clinical Islet Transplantation Consortium: The CIT-08 Study

OBJECTIVE To determine long-term outcomes for islet-alone and islet-after-kidney transplantation in adults with type 1 diabetes complicated by impaired awareness of hypoglycemia. RESEARCH DESIGN AND METHODS This was a prospective interventional and observational cohort study of islet-alone (n = 48) and islet-after-kidney (n = 24) transplant recipients followed for up to 8 years after intraportal infusion of one or more purified human pancreatic islet products under standardized immunosuppression. Outcomes included duration of islet graft survival (stimulated C-peptide >= 0.3 ng/mL), on-target glycemic control (HbA(1c) <7.0%), freedom from severe hypoglycemia, and insulin independence. RESULTS Of the 48 islet-alone and 24 islet-after-kidney transplantation recipients, 26 and 8 completed long-term follow-up with islet graft function, 15 and 7 withdrew from follow-up with islet graft function, and 7 and 9 experienced islet graft failure, respectively. Actuarial islet graft survival at median and final follow-up was 84% and 56% for islet-alone and 69% and 49% for islet-after-kidney (P = 0.007) with 77% and 49% of islet-alone and 57% and 35% of islet-after-kidney transplantation recipients maintaining posttransplant HbA(1c) 90% in both cohorts. Insulin independence was achieved by 74% of islet-alone and islet-after-kidney transplantation recipients, with more than one-half maintaining insulin independence during long-term follow-up. Kidney function remained stable during long-term follow-up in both cohorts, and rates of sensitization against HLA were low. Severe adverse events occurred at 0.31 per patient-year for islet-alone and 0.43 per patient-year for islet-after-kidney transplantation. CONCLUSIONS Islet transplantation results in durable islet graft survival permitting achievement of glycemic targets in the absence of severe hypoglycemia for most appropriately indicated recipients having impaired awareness of hypoglycemia, with acceptable safety of added immunosuppression for both islet-alone and islet-after-kidney transplantation