Comparison of fibrin sealant and staples for attaching split-thickness autologous sheet grafts in patients with deep partial- or full-thickness burn wounds: a phase 1/2 clinical study.

We undertook a multicenter, randomized, controlled, phase 1/2 clinical study to investigate the safety and efficacy of a fibrin sealant containing 4 IU/ml thrombin (FS 4IU) for the attachment of autologous sheet grafts in patients with deep partial-thickness or full-thickness burn wounds. Fibrin sealant (FS 4IU) was compared with staples for adherence of sheet grafts in 40 patients. Patients had to have burn wounds measuring 40% TBSA or less with two comparable test sites measuring between 1% and 4% TBSA each. Wound beds were prepared before treatment assignment, which was randomized. Percent area of hematoma/seroma at Day 1 (P = .0138) and questionable viability at Day 5 (P = .0182) were significantly less for FS 4IU-treated sites. Median percent area of graft survival on Day 14 was 100% for both treatments (P = .3525). The percentage of completely closed sites generally was greater for FS 4IU-sites on Days 5 to 91; the maximum difference occurred at Day 28 (79.5% vs 59%; P = .0215). The safety profile of FS 4IU was excellent as indicated by the lack of any related serious adverse experiences. These findings indicate that FS 4IU is safe and effective for fixation of skin grafts, with outcomes similar to or better than staple fixation. The data suggest that FS 4IU is a promising candidate for further clinical studies focusing on skin graft adhesion and burn wound healing.

Infrared tympanic thermometry in comparison with other temperature measurement techniques in febrile children.

OBJECTIVE: : To determine whether infrared tympanic thermometry (ITT) measurements more accurately reflect core body temperatures than axillary, forehead, or rectal measurements during fever cycles in children. DESIGN: : Prospective cohort study. SETTING: : Pediatric and cardiac intensive care units at a tertiary care children's hospital. PATIENTS: : Critically ill children <7 yrs of age with indwelling bladder catheters. INTERVENTIONS: : Simultaneous temperatures were recorded during both febrile and nonfebrile periods using ITT, indwelling bladder (core), axillary, forehead, and indwelling rectal measurements in 36 children. MEASUREMENTS AND MAIN RESULTS: : Overall ITT measurements were 0.03 +/- 1.43 degrees F less than core temperature measurements. In comparison, rectal, forehead, and axillary measurements averaged 0.62 +/- 1.44, 0.56 +/- 1.81, and 1.25 +/- 1.73 degrees F less than core temperature measurements. ITT measurements had better agreement with core measurements during increasing and decreasing temperature cycles. Receiver operating characteristic analysis performed on increasing and decreasing temperature cycle data revealed that ITT measurements performed well, with an area under the curve of 0.855 (95% confidence interval, 0.797-0.913) in comparison with rectal measurement area under the curve of 0.777 (95% confidence interval, 0.701-0.853), forehead measurement area under the curve of 0.710 (95% confidence interval, 0.715-0.888), and axillary measurement area under the curve of 0.664 (95% confidence interval, 0.579-0.750). CONCLUSIONS: : ITT measurements more accurately reflect core temperatures than any other measurement site during febrile and nonfebrile periods in children. ITT measurements are a reproducible and relatively noninvasive substitute for bladder or rectal measurements in febrile children.

Assessing parallelism prior to determining relative potency.

In the course of preparing a revision to Chapter (111) of the U.S. Pharmacopeia, the revision committee came to a unanimous agreement that the method for assessing parallelism that is currently presented in (111) and in the European Pharmacopeia's Chapter 5.3 is flawed and should be replaced. The symptoms are that perfectly acceptable assay results may fail due to good precision and that obviously faulty assay results may pass due to poor precision. The flaw is that the wrong statistical technique has been used. We propose an alternative approach based on the equivalence testing paradigm that does not have these shortcomings. Equivalence testing requires the establishment of equivalence limits. Specific approaches for establishing equivalence limits are discussed.

Validation of the CNS emotional lability scale for pseudobulbar affect (pathological laughing and crying) in multiple sclerosis patients.

Pseudobulbar affect (PBA) or pathological laughing and crying (PLC) is a disorder of affect that occurs in about 10% of multiple sclerosis (MS) patients. The objective of this study was to validate the CNS Emotional Lability Scale (CNS-LS) in MS patients and to correlate the results with the frequency and intensity of episodes of PLC. Physicians at seven private practice referral centers in the United States made a diagnosis concerning PLC based on patient interviews. Clinical coordinators separately administered the CNS-LS, a self-report measure of PLC with seven questions, to MS patients, including patients known to exhibit PLC, patients thought to be free of PLC, and newly diagnosed patients where PLC status was unknown, and the physician was blinded as to the results. A receiver operating characteristic (ROC) curve analysis was performed to define a cut-off best correlating with the physician's diagnosis. Of 90 MS patients selected to complete the survey, 50 were physician diagnosed with PLC; 40 were without PLC, and 15 of these 90 patients were newly diagnosed with MS (<6 months). Scores of 17 or higher corresponded to a sensitivity of 0.94 and a specificity of 0.83 (LR+ = 5.5, LR- = 0.07); 89% of patients were correctly diagnosed. The area under the ROC curve was 0.95. Symptoms were greater in patients diagnosed as PLC than in non-PLC patients as evidenced by mean number of episodes/week, number of days/week with episodes, duration of an episode and total time in an episode. Similar results were observed if patients were classified as PLC or non-PLC according to CNS-LS score > or = 17, suggesting that the CNS-LS is a valid measure for the assessment of PLC in MS patients and could be a useful instrument for clinical and research purposes.

Diagnostic accuracy and cost-effectiveness of contrast echocardiography on evaluation of cardiac function in technically very difficult patients in the intensive care unit.

Echocardiographic assessment of cardiac function can be quite difficult in the intensive care unit and may require transesophageal echocardiography (TEE). We therefore compared harmonic imaging alone or in combination with contrast to TEE in 32 consecutive patients in the intensive care units who were considered technically very difficult (> or =50% of the 16 segments not visualized from any view). Excellent or adequate endocardial visualization was achieved in 13% of segments with fundamental imaging, 34% with harmonic imaging, and 87% with contrast (p < 0.0001); the latter success rate was similar to TEE (87% vs 90%; p = NS). When TEE was used as the standard, agreement in exact interpretation of wall motion increased from 48% for fundamental imaging to 58% with harmonic imaging, and reached 70% with contrast (p <0.0001). Contrast had the best sensitivity (89%) for detecting wall motion abnormalities. Estimation of ejection fraction was possible in 31% with fundamental imaging, 50% with harmonic imaging, and in 97% with contrast. Ejection fraction quantitated by contrast enhancement correlated best with TEE (r = 0.91). Cost-effectiveness analysis revealed that contrast echo was cost-effective compared with TEE in determining regional and global ventricular function, with a cost saving of 3% and 17%, respectively. Thus, contrast echocardiography provides an accurate, safe, and cost-effective alternative to TEE for evaluating ventricular function in technically very difficult studies.