Barazone decreases skin lesions and pruritus and increases quality of life in dogs with atopic dermatitis: a randomized, blinded, placebo-controlled trial.

A randomized, blinded, placebo-controlled study was conducted to assess the efficacy of a new 0.025% budesonide leave-on-conditioner (Barazone) in controlling the clinical signs of canine atopic dermatitis (AD). Twenty-nine dogs with AD were randomly allocated to receive 3 weeks of once-weekly treatment with either Barazone or Placebo and then were crossed-over to receive the alternative treatment for a further 3 weeks. At the start and end of each treatment phase, referring veterinarians performed a dermatological and general physical examination on each dog, assigned a Lesional Score, collected blood for haematological and biochemical analyses and rated the dog's overall tolerance to the preceding treatment. Owners assessed their dog's level of pruritus and quality of life (QoL) daily, using visual analogue scales labelled with behavioural descriptors. Barazone improved skin lesions (P = 0.02) and QoL (P < 0.001) and reduced pruritus (P ≤ 0.002) compared with treatment with Placebo. There were no significant differences in the tolerance scores and only minor differences in the general physical examination findings and haematological and biochemical parameters between dogs receiving Barazone or Placebo. This study demonstrated that Barazone, applied once weekly at 1 g/kg for 3 weeks, was an efficacious treatment for the control of the clinical signs of AD in dogs.

The effects of freezing skin on transdermal drug penetration kinetics.

This study investigated the effects of freezing canine skin on the penetration kinetics of hydrocortisone. Skin samples from three dogs were used for in vitro penetration studies commencing on the day of skin collection (fresh skin) and again after freezing at -20 degrees C for 1, 4, 8 and 12 months. When the data from the dogs was averaged, the pseudo-steady-state flux (Jss) of hydrocortisone through skin frozen for any duration was significantly (P < 0.023) greater than through fresh skin and there was a positive relationship (P < 0.007) between the length of freezing and DeltaJss. For all dogs, the lag times (tlag) calculated for hydrocortisone penetration were significantly (P < 0.029) shorter through skin that had been frozen, compared with fresh skin. However, the shapes of the permeation profiles of hydrocortisone appeared similar through the fresh and frozen dog skins and no differences were detected between the groups on histological examination. The results of this study have shown that freezing dog skin at -20 degrees C can significantly increase the transdermal penetration of hydrocortisone in vitro, and that the extent of this enhancement can increase with duration of freezing.

Ototoxicity and tolerance assessment of a TrisEDTA and polyhexamethylene biguanide ear flush formulation in dogs.

Clinically healthy mixed breed dogs (n = 20) were used to determine if a Tris (tromethamine)-buffered test solution, Otinide (Trademark of Dermcare-Vet Pty-Ltd, Australia), containing disodium ethylenediamine tetraacetic acid (EDTA; 1.21 g/L) and polyhexamethylene biguanide (PHMB; 0.22 g/L) caused ototoxicity or vestibular dysfunction. The dogs were randomly assigned to either a control group (group A, n = 10) receiving saline, or a treatment group (group B, n = 10) receiving the test solution. Phase 1 of the study consisted of applying 5.0 mL of saline to both ears of the control group (group A) and 5 mL of test solution to both ears of the test group (group B), for 21 days. A bilateral myringotomy was then performed on each dog under deep sedation. Phase 2 of the study then consisted of applying 2.0 mL of the saline to both ears of the control group (group A) and 2.0 mL of the test solution to both ears of the test group (group B), for 14 days. Throughout the study, dogs were examined for clinical health, and underwent otoscopic, vestibular and auditory examinations. The auditory examinations included brainstem auditory evoked potential (BAEP) threshold and supra-threshold assessments using both click and 8 kHz tone burst stimuli. The absence of vestibular signs and effects on the BAEP attributable to the test solution suggested the test solution could be applied safely to dogs, including those with a damaged tympanic membrane.

A parametric estimation procedure for relapse time distributions.

In a relapse clinical trial patients who have recovered from some recurrent disease (e.g., ulcer or cancer) are examined at a number of predetermined times. A relapse can be detected either at one of these planned inspections or at a spontaneous visit initiated by the patient because of symptoms. In the first case the observations of the time to relapse, X, is interval-censored by two predetermined time-points. In the second case the upper endpoint of the interval is an observation of the time to symptoms, Y. To model the progression of the disease we use a partially observable Markov process. This approach results in a bivariate phase-type distribution for the joint distribution of (X, Y). It is a flexible model which contains several natural distributions for X, and allows the conditional distributions of the marginals to smoothly depend on each other. To estimate the distributions involved we develop an EM-algorithm. The estimation procedure is evaluated and compared with a non-parametric method in a couple of example based on simulated data.

Validation testing of the spacelabs PC2 ST-segment analyzer.

OBJECTIVES: Recent studies have demonstrated that perioperative myocardial ischemia, detected by electrocardiography, is a risk factor for myocardial infarction. ST-segment analyzers and hemodynamic monitors may be useful for on-line detection in perioperative and critical care environments. However, independent performance and accuracy standards for these devices have not been established. Therefore, a testing protocol was developed using an electrocardiogram (ECG) simulator that allowed selectively altered ST-segment displacement, in a calibrated fashion over a wide range. DESIGN: Laboratory bench study. SETTING: Not applicable. PARTICIPANTS: Not applicable. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Custom digital ECG waveform templates were programmed for use with a commercially available ECG simulator (M311 ECG simulator; Fogg Systems, Inc., Aurora, CO). For each template, ST-segment morphology (horizontal elevation or depression, downsloping depression), QRS duration, and the presence or absence of a P wave were manipulated, resulting in seven different QRS shapes. Within each shape, the degree of ST-segment deviation was altered over a wide range. A PC2 Bedside Monitor (SpaceLabs Inc., Redmond, WA) was tested. One hundred forty-eight measurements of ST-segment deviation input from the simulator were made at each of two testing sessions. The first ST-segment value displayed by the analyzer was recorded, and the two measurements averaged for comparison. Placement of the J-point, J + 60 msec, and isoelectric reference points by the analyzer were evaluated. Simulator output was validated for accuracy and stability. Subtle errors in placement of the J-point marker were observed in all seven QRS shapes. These errors usually did not alter placement of the isoelectric marker before, but not exactly at the beginning of, the R-wave upstroke. Thus, ST-segment values returned by the monitor (J + 60 msec - isoelectric reference value) were unaffected. However, in two QRS shapes, the isoelectric point was displaced onto the upstroke of the R wave, resulting in erroneous ST-segment values. In one, the error may have been caused by the difference in QRS duration of that template (120 msec) relative to the fixed 115-msec interval from the J point used by the analyzer and was present in all points tested. In the second (normal QRS duration), the error was present in some, but not all points tested (4/21, 24%). All QRS shapes with proper placement of the isoelectric point returned ST-segment values within +/- 0.5 mm of expected, and 98% were within +/- 0.25 mm of expected. The mean difference between observed and expected ST-segment values for 100 measurements with normal QRS duration and proper isoelectric point placement was 0.08 mm +/- 0.07 mm (SD). CONCLUSIONS: The bench results suggest that visual confirmation of ST-segment analyzer values may be advisable in the clinical setting. Although most complexes with normal conduction and a P wave are likely to be accurately analyzed, those with prolonged QRS duration were problematic. The simulator protocol may be helpful in ensuring accuracy of ST-segment analyzers, especially in their early development stages.