Improving the safety of neuromuscular blocking agents: a statement from the USP Safe Medication Use Expert Committee.

PURPOSE: Recommendations of the interdisciplinary Safe Medication Use Expert Committee of the United States Pharmacopeia (USP) to assist health care professionals, manufacturers, and organizations in handling neuromuscular blocking agents (NMBAs) safely and effectively are discussed. SUMMARY: Review and analysis of the USP Medication Errors Reporting Program and MEDMARX program databases showed a continuing risk of patient harm or death due to errors with NMBAs. Medication errors involving wrong concentrations, wrong doses, wrong drugs, look-alike packaging, and sound-alike names, combined with lack of monitoring and communication, have been associated with the use of NMBAs in health care institutions. Serious adverse events occur when NMBAs are used without adequate safeguards. Recommendations for improving safety were developed through review and discussion of root causes and areas of concern with these medications. CONCLUSION: Medical errors with NMBAs continue to result in patient morbidity and mortality. Increased awareness and action on the part of all parties involved are needed to improve the safety of this class of medications.     

In vitro/in vivo functionality of Catapres-TTS

The in vitro and in vivo functionality of Catapres-TTS, a transdermal therapeutic system that delivers the alpha adrenergic receptor agonist clonidine, is discussed in terms of the drug transport kinetics and resultant plasma drug concentration profiles. The design of Catapres-TTS is presented as an optimization by which the best combination of system performance characteristics is obtained within the inherent limitations of the transdermal drug transport properties and the known pharmacokinetic and pharmacodynamic properties of the drug. Clonidine is a potent antihypertensive agent with a relatively low therapeutic index. For Catapres-TTS, the majority of control over the drug input rate resides within the system, rather than within the skin, which significantly reduces the variability in drug input rate and resulting plasma drug concentration both within and between patients. Moreover, the presence of a rate-control element in the system allows for patterning of the drug release rate. An initial bolus of drug is placed in the contact adhesive layer, where its transport into the skin is not inhibited by the rate control element in the system, for reduction in the time needed to achieve steady state drug input. The selection of the loading dose of drug is described as an optimization between the minimization of the lag time and the maintenance of constant plasma drug concentrations during the crossover period between system applications in chronic therapy.     

A schema-focused approach to group psychotherapy for outpatients with borderline personality disorder: A randomized controlled trial

This study tests the effectiveness of adding an eight-month, thirty-session schema-focused therapy (SFT) group to treatment-as-usual (TAU) individual psychotherapy for borderline personality disorder (BPD). Patients (N = 32) were randomly assigned to SFT-TAU and TAU alone. Dropout was 0% SFT, 25% TAU. Significant reductions in BPD symptoms and global severity of psychiatric symptoms, and improved global functioning with large treatment effect sizes were found in the SFT-TAU group. At the end of treatment, 94% of SFT-TAU compared to 16% of TAU no longer met BPD diagnosis criteria (p < .001). This study supports group SFT as an effective treatment for BPD that leads to recovery and improved overall functioning.     

Benzodiazepine ([3H]flunitrazepam) binding in cat visual cortex: ontogenesis of normal characteristics and the effects of dark rearing

[3H]Flunitrazepam (FNZ) binding sites were characterized in homogenates of cat visual cortex during normal postnatal development and following dark rearing from birth. In parallel experiments, the distribution and density of [3H]FNZ binding sites were examined by in vitro autoradiographic or 'scrape' methods. In homogenates, Bmax measurements showed low early values, rising to a peak in receptor density at about 60 days postnatal, followed by a decline in adulthood. At all ages, gamma-aminobutyric acid (GABA) altered the Kd, but not the Bmax of [3H]FNZ binding sites. Kd values showed a general increase with age, parallelled by an increased sensitivity to GABA. Receptor autoradiography revealed that the highest density of [3H]FNZ binding sites was in layer IV of cats of all ages. Deafferentation of extrinsic inputs to the visual cortex by surgical undercutting did not alter this pattern of laminar distribution, indicating that the receptors were associated with intrinsic cortical elements rather than subcortical inputs. Dark rearing had no effect on [3H]FNZ laminar distribution in the visual cortex. The Bmax was higher at 30 days postnatal, but did not differ significantly thereafter. Modulation by GABA was concomitantly higher at 30 days, but lower than normal in dark-reared animals at ages greater than 30 days postnatal. The results are discussed in relation to the normal and abnormal development of GABA receptors in the cat visual cortex.     

Orthotopic placement of the dunning R3327 AT-3 prostate tumor in the copenhagen X fischer rat

Orthotopic placement of in vitro propagated Dunning R3327 AT-3 tumor cells resulted in a greater percentage of tumor takes and a two-fold shift in the exponential growth curve compared to flank implantation. The orthotopic tumor appeared to disseminate preferentially to regional lymph nodes, rather than to the lungs which is characteristic of flank tumors. The results suggest an important role of stromal-epithelial interactions in the growth of this tumor. © 1995 Wiley-Liss, Inc.     

FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.     

Methodological considerations in the study of parental occupational exposures and congenital malformations in offspring

The existence of hazardous substances in the workplace has raised concerns about the potential of these substances for adverse reproductive effects. Identification of associations between parental occupational exposures and congenital malformations in the offspring may provide the opportunity for preventing such exposures and thus reduce the risk of malformations. However, there are many methodological considerations inherent in studying the potential relation between parental occupational exposures and congenital malformations in the offspring. Considerations relating to outcome include methods and timing of ascertaining cases with malformations, diagnostic criteria, and problems in grouping malformations for purposes of analysis. With regard to measuring exposures, issues include methods for obtaining valid estimates of the nature, duration, timing of exposure, and exposure-response relationship. Other methodological issues discussed include selection of appropriate reference groups, sample size, and multiple hypothesis testing.     

Urodilatin, not nitroprusside, combined with dopamine reverses ischemic acute renal failure.

The present study was undertaken to: (a) clarify the comparative renal potency of bolus injection of the natriuretic peptides urodilatin and ANF99-126 in the rat; (b) establish whether or not intravenous (i.v.) infusion of urodilatin (200 ng/min) combined with dopamine (UD) to maintain mean arterial pressure could improve GFR or renal histology in established experimental ischemic acute renal failure (ARF) induced by 30 minutes of bilateral renal artery clamping; (c) assess comparative efficacies of nitroprusside, an activator of soluble guanylate cyclase, combined with dopamine (ND) or control infusions of dopamine alone (DA), under equivalent conditions; and (d) determine effects of intra-renal arterial infusions of the stable cGMP analogue dibutyryl-cGMP immediately after renal artery clamping (RAC). After initial dose finding studies, i.v. infusion of UD 24 hours after 30 minutes of RAC improved GFR over five hours from 0.24 +/- 0.04 to 1.0 +/- 0.16 ml/min in association with a threefold rise in plasma cGMP and a 13-fold increase in urinary cGMP excretion. Plasma creatinine dropped by 41% from 230 +/- 16 to 135 +/- 18 microM/liter and was still reduced 24 hours later with values averaging 106 +/- 14 compared to 274 +/- 53 microM/liter in non-treated animals. During infusion, UV and FENa+ increased from 1.4 +/- 0.2 to 8.3 ml/min, and from 2.9 +/- 0.5 to maximum values of 15.8 +/- 2.4%. ND or DA alone were less effective, increasing GFR only to 14 and 20%, respectively, of normal values, but improvements were not sustained; in contrast to UD, ND did not alter plasma or urinary cGMP. In addition, DBcGMP was ineffective in improving GFR during early ARF. Histologically UD, but not ND, markedly reduced the incidence of granular casts, tubular desquamation and tubular necrosis in cortical areas and increased the incidence of medullary mitoses.