Evaluation of immunogenicity of LY2963016 insulin glargine compared with Lantus® insulin glargine in patients with type 1 or type 2 diabetes mellitus.

AIMS: To compare the immunogenicity profiles and the potential effects on clinical outcomes of LY2963016 insulin glargine (LY IGlar) and Lantus® insulin glargine (IGlar), products with identical primary amino acid sequences, in patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM). METHODS: To assess immunogenicity, anti-insulin glargine antibodies (measured as percent binding) were compared between treatments in 52-week (open-label) and 24-week (double-blind) randomized studies in total study populations of patients with T1DM (N = 535) and T2DM (N = 756), respectively, and two subgroups of patients with T2DM: insulin-naïve patients and those reporting prestudy IGlar treatment (prior IGlar). Relationships between insulin antibody levels and clinical outcomes were assessed using analysis of covariance and partial correlations. Insulin antibody levels were assessed using Wilcoxon rank sum. Treatment comparisons for treatment-emergent antibody response (TEAR) and incidence of detectable antibodies were analysed using Fisher's exact test. RESULTS: No significant treatment differences were observed for insulin antibody levels, incidence of detectable anti-insulin glargine antibodies, or incidence of TEAR [overall and endpoint, by last-observation-carried-forward (LOCF)] in patients with T1DM or patients with T2DM, including the insulin-naïve subgroup. A statistically significant difference was noted in the overall incidence of detectable antibodies but not at endpoint (LOCF) nor in TEAR for the prior IGlar subgroup of patients with T2DM. Insulin antibody levels were low (<5%) in both treatment groups. Insulin antibody levels or developing TEAR was not associated with clinical outcomes. CONCLUSIONS: LY IGlar and IGlar have similar immunogenicity profiles; anti-insulin glargine antibody levels were low for both treatments, with no observed effect on efficacy and safety outcomes.

Investigation and management of an epidemic of Hydroview intraocular lens opacification.

BACKGROUND: Opacification of Hydroview posterior chamber intraocular lenses had been prescribed, but many aspects of this complication remain unknown, including its aetiology, clinical features, pathogenesis, prognosis and treatment. This paper describes an epidemic of Hydroview intraocular lens (IOL) opacification. METHODS: Subjects in whom the Hydroview IOL was implanted were recalled for evaluation of its transparency, assessment of contrast sensitivity (CS) [VCTS (Vistech CO, Dayton, Ohio, USA)] and visual acuity (LogMAR), and analysis of medical and surgical data. The results of IOL exchange in 69 eyes of 67 patients are also presented. RESULTS: Of 103 patients recalled, 46 (44.6%) and 3 (2.9%) exhibited opacification of the implanted IOL in one and both eyes, respectively. CS was significantly worse in the presence of an opacified IOL (P<0.050), even when Snellen acuity was unaffected. Where the viscoelastic employed during the primary cataract surgery was reliably documented, VISCOAT was used in 100% of cases (43/43), whereas Healonid had not been used in any (0/57) (P<0.0001). Following IOL exchange, visual acuity improved from a mean (+/-SD) of 0.75 (0.41) to 0.4 (0.34) LogMAR. CONCLUSIONS: The prevalence of Hydroview IOL opacification is associated with the use of VISCOAT in the primary cataract surgery, and there is a biochemically plausible rationale to account for this. Visual acuity and contrast sensitivity are adversely affected by opacification of the Hydroview IOL, but CS to a greater extent. Exchange of opaque IOLs is a visually rewarding procedure.

Thrombin generation in non-cardioembolic stroke subtypes: the Hemostatic System Activation Study.

BACKGROUND: The association between hemostatic activation, stroke mechanism, and outcome is poorly defined. The Hemostatic System Activation Study (HAS) investigators measured serial levels of prothrombin fragment F1.2, a marker of thrombin generation, in patients enrolled in the Warfarin Aspirin Recurrent Stroke Study (WARSS). METHODS: HAS enrolled 631 of the 2,206 patients in WARSS. Strokes were subtyped according to inferred mechanism. Plasma was collected for F1.2 at randomization (within 30 days of stroke), 3 months, 12 months, and 18 months. The 3 to 6 month samples in aspirin-treated patients were used for the primary analysis. RESULTS: The authors analyzed 3 to 6 month samples on 320 patients. Higher F1.2 levels were associated with older age, female sex, and hypertension. There was no difference between mean F1.2 levels in 56 cryptogenic (0.9 +/- 0.32 nmol/L) and 114 non-cryptogenic (1.13 +/- 0.74 nmol/L) patients or across specific stroke subtypes. There was an 8.8%/year (p = 0.006) increase in mean F1.2 levels. There was a trend toward higher risk of recurrent stroke or death as F1.2 levels increased in aspirin (RR: 1.30, 95% CI: 0.57 to 2.94, p = 0.53) and warfarin treated patients (RR: 1.68, 95% CI: 0.48 to 5.94, p = 0.42). F1.2 levels were reduced on average 70% in warfarin-treated patients in a dose-dependent fashion. CONCLUSION: F1.2 levels did not appear to differ by stroke subtype, suggesting that factors other than underlying stroke pathophysiology influence thrombin generation in the post-acute stroke period. F1.2 levels were suppressed by warfarin in a dose-dependent fashion. Additional research is needed to determine the predictive value of F1.2 after stroke.

Assessing ADHD across settings: contributions of behavioral assessment to categorical decision making.

Adapted methods of behavioral assessment to assess home and school functioning in a way that maps directly to the Diagnostic and Statistical Manual of Mental Disorders (4th ed., [DSM-IV]; American Psychiatric Association, 1994). The study was conducted in a school-based sample with 5- to 12-year-old children referred to a school intervention team. A multigate set of procedures was used to assign children to one of 3 groups: attention deficit hyperactivity disorder (ADHD), inattentive group; ADHD, combined group; and a non-ADHD control group. The ADHD Rating Scale-IV was used to assess parent and teacher ratings of ADHD symptoms as delineated in DSM-IV. The findings suggest that the use of a fixed cutoff point (i.e., 6 or more symptoms), which is employed in the DSM-IV, is often not the best strategy for making diagnostic decisions. The optimal approach depends on whether diagnostic information is being provided by the parent or teacher and whether the purpose of assessment is to conduct a screening or a diagnostic evaluation. Also, the results indicate that a strategy that aggregates symptoms in the order in which they are accurate in predicting a diagnosis of ADHD is a more effective strategy than the approach used in DSM-IV, which aggregates any combination of a specific number of items. Implications for using methods of behavioral assessment to make diagnostic decisions using DSM-IV criteria are discussed.

Degree of revascularization in patients with multivessel coronary disease: a report from the National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry.

There is controversy regarding the application of angioplasty to patients with multivessel disease in whom all significant stenoses are not dilated. We analyzed the outcomes of 286 patients with multivessel disease and prior successful angioplasty at a mean follow-up duration of 26.2 months. End points analyzed included death, myocardial infarction, late revascularization, and angina pectoris. After successful angioplasty, 127 patients had no residual stenoses of 70% or greater (group 1) and 159 patients had one or more residual stenoses of 70% or greater (group 2). Because there were significant differences in baseline risk factors between the two groups, a logistic regression model was used to make the necessary adjustments in the analysis. Adjusted estimates of the risk of death, death/myocardial infarction, or presence of angina pectoris did not differ between the two groups. Group 2 patients, however, had more coronary artery bypass surgery during follow-up, while those in group 1 had more second PTCA procedures. Results suggest that angioplasty can be safely applied to patients with multivessel disease, even when all significant stenoses are not dilated.