Pharmacokinetics of FK506 after intravenous and oral administration in patients awaiting renal transplantation.

The authors examined the safety and pharmacokinetics of FK506, a new hepatically metabolized immunosuppressant, after single-dose intravenous (i.v.) infusion (20 micrograms.kg(-1) x 4 hours-1) and oral (80 micrograms/kg) administration in six nondialysis patients, aged 27 to 53 years, with chronic renal failure awaiting transplantation. A two-period, randomized, crossover study protocol was used with blood samples drawn for 72 hours after each dose and a washout period of 4 days. Whole-blood FK506 levels were determined using a standard, two-step, nonspecific enzyme immunoassay. There were no significant changes in vital signs, EKG, or complete laboratory test battery for any patient during the entire study period. No side effects were noted after i.v. or oral FK506 dosing. Mean +/- SD distribution half life was 0.9 +/- 0.2 hours, elimination half life (t1/2 beta) 33 +/- 8 hours, total body clearance (CL) 2.4 +/- 1.1 L/hour, and bioavailability 14 +/- 12%. There was no significant correlation between serum creatinine (Cr) and CL (r = 0.36) or between Cr and t1/2 beta (r = -0.30). It was found that FK506 is incompletely and erratically absorbed after oral administration and is rapidly distributed outside the blood compartment after IV dosing. An extended sampling period seems necessary to accurately characterize the slow elimination phase of FK506.

Short- and long-term retention of a nursing home education program on metered-dose inhaler technique.

OBJECTIVE: To evaluate an education program on metered-dose inhaler (MDI) technique designed for nurses and trained medication aides (TMAs). DESIGN: The education program included a handout, a lecture incorporating a videotape on correct inhaler and device technique, and hands-on experience with placebo inhalers. The participants' ability to verbalize and demonstrate correct MDI technique was assessed by the same two-person teams before, immediately after, and two months after the program. SETTING: Five nursing homes. PARTICIPANTS: Fifty-six nurses and TMAs practicing in nursing homes. MAIN OUTCOME MEASURES: Learning and retention. RESULTS: The participants' mean (+/- SD) verbal and demonstration scores increased immediately after the program by 68 +/- 18 points for verbalization and 47 +/- 16 points for demonstration. The participants were always better at demonstrating than verbalizing MDI technique. The participants' baseline verbal and demonstration scores correlated with the amount learned. Learning was influenced by the individual nursing home (verbal and demonstration) and personal use (demonstration only), but not by academic degree, previous training, past instruction of a patient, or current care of a patient who was receiving inhaler therapy. After two months, the scores were lower than immediately after the program test by 0-92 points for verbalization and 10-80 points for demonstration; however, the mean scores were still significantly greater (p less than 0.05) than the baseline scores. Retention of knowledge on the correct technique was greater for the demonstration component. Retention was influenced only by the nursing home in which the participant worked, and not any of the other variables. CONCLUSIONS: Our structured education program significantly improved inhaler technique; however, to maintain retention of the material, the program should be frequently repeated.

Consistency of evaluators assessing inhaler technique.

Since correct inhaler technique is vital for maximum efficacy, the evaluation of technique in patients or health care professionals involved in education programs or research projects is essential. Inconsistency could lead to confused patients and inaccurate research findings. This study is the first to determine interrater consistency with assessing recitation and demonstration of inhaler technique and, if needed, was designed to improve consistency until 95% agreement was achieved. A checklist for correct inhaler technique was constructed by consolidating information from the literature and package inserts. Initially three evaluators were used, however, a fourth evaluator was added for the last two trials to create teams to improve consistency. Percent agreement, probability and kappa scores were calculated. Six trials evaluating inhaler technique of 56 health care professionals at five different sites, revisions of the checklist, and evaluator teams were required to increase overall percent agreement from 81% to 98%. Agreement increased substantially on the verbal component because of specific changes made in the checklist and the objective nature. Demonstration steps consistently had lower agreement than verbal steps. Agreement on the demonstration component was more difficult because of subjectivity involved in observing a subject actuate the inhaler at the correct time, inhale or exhale slowly, and hold one's breath. The relative rankings of percent agreement and kappa scores were the same, however, kappa scores allowed differentiation of agreement due to chance and ability. To achieve interrater consistency, training and practice are required. Interrater consistency should be achieved to ensure accurate reporting of research results on inhaler technique and education of patients.

Premedication with lorazepam for bronchoscopy under general anaesthesia.

Lorazepam 3 or 4 mg i.m. was given to 100 patients as premedication before bronchoscopy under thiopentone-suxamethonium anaesthesia. Forty-nine of the patients assessed as anxious received oral lorazepam as preoperative night sedation also. Lorazepam was an effective night sedative. Forty-two of the 49 patients slept well and were calm and co-operative in the morning. Following the i.m. injection of lorazepam, 64% of patients had complete lack of recall for 4--10 h following premedication. Only 5% recalled correctly a simple objective test of memory initiated in the anaesthetic room. The frequency of recall was higher in those who consumed alcohol regularly and in females. There was one case of awareness during bronchoscopy in a patient who received only a small dose of lorazepam (2.8 mg per 70 kg). Side-effects were minimal and patient acceptance was impressive. These results show an advance on previous studies using pethidine and diazepam. Further improvement is needed, particularly in adjusting the dose of lorazepam to body weight and to factors such as age, sex and alcohol intake.

Analysis of polychlorinated biphenyls by carbon-13 nuclear magnetic resonance spectroscopy.

A technique is presented for the analysis of polychlorinated biphenyl mixtures by assigning 13C resonances to the observed peaks and matching these shifts to the shifts of known individual polychlorinated biphenyls. The technique has not proved to be as useful for heavily chlorinated mixtures.