Evaluation of Quantitative Computed Tomography Cortical Hip Quadrant in a Clinical Trial With Rosiglitazone: A Potential New Study Endpoint.

Quantitative computed tomography (QCT) measurements have been used extensively to ascertain information about bone quality and density due to the 3-dimensional information provided and the ability to segment out trabecular and cortical bones. QCT imaging helps to improve our understanding of the role that each bone compartment plays in the pathogenesis and prognosis of fracture. This study was conducted to explore longitudinal changes in femoral neck (FN) cortical bone structure using both volumetric bone mineral density (vBMD) and cortical shell thickness assessments via QCT in a double-blind, randomized, multicenter clinical trial in postmenopausal women with type 2 diabetes mellitus. This study also examined whether treatment-associated changes in the cortical bone vBMD and thickness in femoral neck quadrants could be evaluated. Subjects were randomized to rosiglitazone (RSG) or metformin (MET) for 52 wk followed by 24 wk of open-label MET. A subset of 87 subjects underwent QCT scans of the hip at baseline, after 52 wk of double-blind treatment, and after 24 wk of treatment with MET using standard full-body computed tomography scanners. All scans were evaluated and analyzed centrally. Cortical vBMD at the FN was precisely segmented from trabecular bone and used to assess a possible therapeutic effect on this bone compartment. QCT analysis showed reductions in adjusted mean percentage change in vBMD and in absolute cortical thickness occurred with RSG treatment from baseline to week 52, whereas changes with MET were generally minimal. The reductions observed during RSG treatment for 1 yr appeared to partially reverse during the open-label MET phase from weeks 52 to 76. The femoral neck quadrant may provide utility as a potential endpoint in clinical trials for the understanding of the therapeutic effect of new entities on cortical bone vs trabecular bone; however, further clinical validation is needed. TRIAL REGISTRATION: The protocol (GSK study number AVD111179) was registered on ClinicalTrials.gov as NCT00679939.

Anaphylaxis Triggers and Treatments by Grade Level and Staff Training: Findings from the EPIPEN4SCHOOLS Pilot Survey.

This pilot survey was designed to evaluate the characteristics of anaphylactic events and epinephrine autoinjector (EAI) use in children in U.S. schools. A cross-sectional, web-based, pilot survey of schools participating in the EPIPEN4SCHOOLS® program (Mylan Specialty L.P., Canonsburg, PA) assessed characteristics of anaphylactic events and EAI use during the 2013-2014 academic year. Respondents reported 757 anaphylactic events experienced by students; student grade level was noted for 724 events. Of these events, 32.3% (234/724) were experienced by students in grade school, 18.6% (135/724) by students in middle school, and 49.0% (355/724) by students in high school. Frequency of food-related triggers was consistently high across grade levels. However, many events experienced by students in high school (22.3%, 79/355), middle school (15.0%, 20/135), and grade school (14.1%, 33/234) had an unknown trigger. In 36.0% of schools (2008/5579), only the school nurse and select staff received training to recognize anaphylaxis; most staff or all staff received training in 28.9% (1610/5579) and 30.9% (1722/5579) of schools, respectively. In a majority of schools (54.2%, 3003/5544), only the school nurse and select staff were permitted to administer epinephrine, whereas most staff or all staff were permitted to administer epinephrine in 15.8% (876/5544) and 21.9% (1212/5544) of schools, respectively. Risk of anaphylaxis may be particularly high during adolescence, and some students encounter staff members who are untrained in anaphylaxis recognition or management, or both. These findings support the need for continued anaphylaxis training for the protection of all students, staff, and visitors.

EpiPen4Schools pilot survey: Occurrence of anaphylaxis, triggers, and epinephrine administration in a U.S. school setting.

BACKGROUND: Although epinephrine is the treatment of choice for anaphylaxis, it remains underused. OBJECTIVE: This study was designed to describe anaphylactic events and epinephrine autoinjector (EAI) use in U.S. schools enrolled in the EpiPen4Schools program. METHODS: This exploratory, cross-sectional, Web-based survey of 6019 schools that participated in the EpiPen4Schools program assessed anaphylactic events and EAI use at responding schools during the 2013-2014 school year. RESULTS: A total of 919 anaphylactic events were reported in 607 schools. Of the 852 anaphylactic events with data on those who experienced an event, most 88.8% (n = 757) occurred in students, and 21.9% of events (n = 187) occurred in individuals with no known allergies. Of the 851 events with data on EAI use, 74.7% (n = 636) were treated with EAIs and 8.5% (n = 54) received a second epinephrine injection. Of the 204 individuals not treated with an EAI, 77.0% (n = 157) received antihistamines, 12.7% (n = 26) received another treatment, and 8.3% (n = 17) received no treatment. Of the 850 events with data on hospital transport, 79.6% of individuals (n = 677) were transported to the hospital. Common triggers varied seasonally, with food listed most frequently overall (62.5%). CONCLUSION: More than one in ten schools that participated in the EpiPen4Schools survey reported an anaphylactic event. Approximately 25% of individuals with anaphylactic events were not treated with EAIs, and 20.4% of patients were not taken to the hospital after an anaphylactic event. Analysis of these data supports the value of stocking EAIs and of providing continuing education regarding the recognition and proper treatment of anaphylaxis for school personnel.

Reductions in biomarkers of cardiovascular risk in type 2 diabetes with rosiglitazone added to metformin compared with dose escalation of metformin: an EMPIRE trial sub-study.

OBJECTIVE: To compare the effects of rosiglitazone added to metformin with dose escalation of metformin on cardiovascular risk biomarkers in type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: Cardiovascular biomarkers were assessed in a sub-population of 122 subjects with type 2 diabetes mellitus (mean age 54.6 and 56.0 years, BMI 34.7 and 32.1 kg/m2; for the rosiglitazone plus metformin and metformin groups, respectively) from the multicenter (63 centers in the USA), double-blind, randomized parallel-group Escalation of Metformin theraPy vs. Initiation of Rosiglitazone Early (EMPIRE) study. Treatment group sizes were slightly imbalanced owing to central, rather than local, randomization. Subjects receiving metformin 1000 mg/day at baseline were randomized to rosiglitazone 4 mg/day plus metformin 1000 mg/day (RSG + MET) or metformin 1500 mg/day (up-titrated MET) for 24 weeks. At 8-weeks, rosiglitazone was increased to 8 mg/day in RSG + MET recipients and metformin to 2000 mg/day in up-titrated MET recipients. RESULTS: Reductions from baseline in HbA1c at week 24 (mean +/- SD) occurred in both groups (RSG + MET: -0.61% +/- 1.16%; up-titrated MET: -0.65% +/- 1.18%). Post-prandial glucose levels (AUC(0-3h)) decreased with RSG + MET (-3.5 mmol/L.h; 95% confidence interval [CI]: -5.2 to -1.8) and up-titrated MET (-1.3 mmol/L.h; 95% CI: -3.8 to 1.1). Homeostasis Model Assessment (HOMA)-estimated insulin sensitivity increased by 37.7% (95% CI: 22.8 to 54.5) in RSG + MET and 6.9% (95% CI: -6.2 to 21.9) in up-titrated MET recipients. RSG + MET reduced C-reactive protein (CRP; -23.9%; 95% CI: -40.4 to -2.8), plasminogen activator inhibitor-1 (PAI-1) activity (-30.1%; 95% CI: -44.5 to -11.9), PAI-1 antigen (-15.5%; 95% CI: -28.3 to -0.3) and matrix metalloproteinase-9 (MMP-9; -13.8%; 95% CI: -25.1 to -0.9), but increased tumor necrosis factor-alpha (TNF-alpha; 27.0%; 95% CI: 6.8 to 50.9). Corresponding values for up-titrated MET were CRP -9.3% (95% CI: -36.9 to 30.2), PAI-1 activity -7.2% (95% CI: -28.2 to 20.0), PAI-1 antigen -1.5% (95% CI: -17.4 to 17.5), MMP-9 29.0% (95% CI: -1.3 to 68.6) and TNF-alpha -6.0% (95% CI: -22.0 to 13.2). CONCLUSIONS: These results suggest that rosiglitazone plus metformin has positive cardiovascular effects against a background of similar glycemic improvements.