Cumulative characteristics of atracurium and vecuronium. A simultaneous clinical and pharmacokinetic study

BACKGROUND: Cumulative effects (increased 25-75% recovery time with increasing dose) are evident with vecuronium but not with atracurium. Pharmacokinetic simulations suggest that vecuronium's cumulation occurs as recovery shifts from distribution to elimination whereas atracurium's recovery always occurs during elimination. The purpose of this study was to examine this pharmacokinetic explanation. METHODS: We assigned 12 volunteers to receive atracurium of vecuronium on three occasions during nitrous oxide-isoflurane anesthesia. Evoked adductor pollicis twitch tension was monitored. On occasion 1, the dose expected to produce 95% block (ED95) was estimated for each subject. On occasions 2 and 3, 1.2 or 3.0 multiples of ED95 were given as a bolus. Plasma was sampled for 128 min to determine muscle relaxant concentrations; pharmacodynamic modeling was used to determine effect-compartment drug concentrations (Ce). For each drug, recovery time, recovery phase half-life (rate of decrease in Ce during recovery), and Ce at 25% and 75% recovery were compared between doses. RESULTS: Atracurium's recovery time increased 2.4 +/- 2.2 min (mean +/- SD) with the larger dose, less than the increase with vecuronium (8.2 +/- 3.8 min). Atracurium's recovery phase half-life was 14.6 +/- 1.7 and 20.1 +/- 2.3 min with the small and large doses (P < 0.05); vecuronium's recovery phase half-life increased similarly from 13.5 +/- 2.3 to 18.5 +/- 5.0 min (P < 0.05). At 75% recovery, vecuronium's Ce decreased from 65 +/- 18 ng/ml with the small dose to 55 +/- 15 ng/ml with the large dose (P < 0.05). Assuming that neuromuscular junction sensitivity was constant, this difference could be explained by considering neuromuscular effects of vecuronium's metabolite, 3-desacetylvecuronium. CONCLUSIONS: Although vecuronium was cumulative (as predicted), atracurium was also slightly cumulative. Inconsistent with our hypothesis, recovery phase half-lives for both drugs increased similarly between doses; therefore, differences in cumulation were not solely explained by pharmacokinetics of the muscle relaxant. It appears that 3-desacetylvecuronium contributes to vecuronium's cumulative effect, even after usual clinical doses.     

Delinquent peer affiliation and conduct problems: A twin study.

Many putative environmental risks correlate with individuals' genotypes. The association between delinquent peer affiliation and conduct problems may occur because of shared genetic liability. Five hundred fifty three monozygotic and 558 dizygotic twin pairs, aged 11 to 18 years, were assessed for delinquent peer affiliation and conduct problems. The authors investigated whether genes contribute to both delinquent peer affiliation and the correlation between delinquent peer affiliations and conduct problems. Delinquent peer affiliation was influenced by genetic, shared environmental, and nonshared environmental factors; genetic factors also contributed to the correlation between delinquent peer affiliations and conduct problems, providing evidence for genotype-environment correlation. The magnitude of the genetic variance of conduct problems was contextually dependent on levels of delinquent peer affiliation and was greater at higher levels of delinquent peer affiliation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reflections on replications and the experimenter bias effect.

The value of replications in psychology, the need to distinguish between the probability of data and of hypotheses, and the implications of alternative conceptualizations of the experimenter bias effect (EBE), are discussed in the light of the failure reported by T. X. Barber, et al. (see 43:6) to replicate earlier findings by R. Rosenthal and K. Fode (see 38:3). The position was taken that the value of further research on the EBE will depend upon the prior development of a situational taxonomy and a theoretical formulation in which the effect may be conceptualized in terms of a broader class of phenomena. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Guidelines for the design and conduct of clinical trials on dentine hypersensitivity

Clinical trials on dentine hypersensitivity have been numerous and protocols varied. To date there is little consensus as to the conduct of studies on this poorly-understood yet common and painful dental condition. A committee of interested persons from academia and industry was convened to discuss the subject of clinical trials on dentine hypersensitivity and a consensus report is presented. A double-blind randomized parallel groups design is recommended, although cross-over designs may be used for the preliminary screening of agents. Subjects may have multiple sites scored. Sample size will be determined by estimating the variability in the study population, the effect to be detected and the power of the statistical test to be used. Subject selection is based on a clinical diagnosis of dentine hypersensitivity, excluding those with conflicting characteristics such as currently-active medical or dental therapy. The vestibular surfaces of incisors, cuspids and bicuspids are preferred as sites to be tested. A range of sensitivity levels should be included. Tactile, cold and evaporative air stimuli should be applied. Negative and benchmark controls should be incorporated. Most trials should last 8 weeks. Sensitivity may be assessed either in terms of the stimulus intensity required to evoke pain or the subjective evaluation of pain produced by a stimulus using a visual analog or other appropriate scale. The subject's overall assessment may be determined by questionnaire. Outcomes should be expressed in terms of clinically significant changes in symptoms. Follow-up evaluation is required to determine the persistence of changes. At least 2 independent trials should be conducted before a product receives approval.     

Self-reconstitution processes: A proposal for reorganizing the conduct of confirmed smokers.

Describes the 5 components of a theory of self-reconstitution: symbolic death and rebirth, the group and other, ritual behavior, proprioceptive stimuli, and triggers. A smoking therapy based on this theory and incorporating some of the spiritual exercises of St. Ignatius Loyola and of behavior modification are incorporated into a smoking therapy. The basic paradigm attempts to cure the confirmed smoker of cigarette use in a 2-wk resident program which relies heavily on group pressures and imagining sequences. The conflict between contexualist paradigm implicit in the model and the mechanistic paradigm ordinarily employed by practitioners of the science of behavior is discussed. (25 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Attributes of clinical guidelines that influence use of guidelines in general practice: observational study

OBJECTIVE: To determine which attributes of clinical practice guidelines influence the use of guidelines in decision making in clinical practice. DESIGN: Observational study relating the use of 47 different recommendations from 10 national clinical guidelines to 12 different attributes of clinical guidelines-for example, evidence based, controversial, concrete. SETTING: General practice in the Netherlands. SUBJECTS: 61 general practitioners who made 12 880 decisions in their contacts with patients. MAIN OUTCOME MEASURES: Compliance of decisions with clinical guidelines according to the attribute of the guideline. RESULTS: Recommendations were followed in, on average, 61% (7915/12 880) of the decisions. Controversial recommendations were followed in 35% (886/2497) of decisions and non-controversial recommendations in 68% (7029/10 383) of decisions. Vague and non-specific recommendations were followed in 36% (826/2280) of decisions and clear recommendations in 67% (7089/10 600) of decisions. Recommendations that demanded a change in existing practice routines were followed in 44% (1278/2912) of decisions and those that did not in 67% (6637/9968) of decisions. Evidence based recommendations were used more than recommendations for practice that were not based on research evidence (71% (2745/3841) v 57% (5170/9039)). CONCLUSIONS: People and organisations setting evidence based clinical practice guidelines should take into account some of the other important attributes of effective recommendations for clinical practice.     

Looking for the disorder in conduct disorder.

Besides their well-known externalizing behavior, children with conduct disorder (CD) often have additional impairments outside the criteria for the CD diagnosis. In a 5-year study of 984 treated children (ages 5–17 years), those with CD had an average of 2.2 primary diagnoses. Children with CD showed the worst problem and impairment scores in comparison with 11 common diagnoses. Compared with other treated children, children with CD achieved worse scores on 14 of 15 syndromes, including internalizing problems such as withdrawal and major depression. The average child with CD had larger relapse scores in the 1.5- to 3-year period after admission to treatment. This pattern, pervasive at intake and chronic in course, resembles a global disability more than a circumscribed problem managed with a narrow range of treatments specific to it. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Does the Stepladder Technique improve group decision making? A series of failed replications.

Past research has demonstrated the effectiveness of a structured group decision-making technique, termed the Stepladder Technique, in improving group decisions. The purpose of the present series of studies was to replicate and extend this research. Five studies (three using different tasks than previous studies and two using the same task) compared the decision quality of groups using the self-paced Stepladder Technique to unstructured groups. In all studies, stepladder groups failed to perform better than unstructured groups. This failure to replicate and extend past research suggests that there are definite boundaries, such as the sample or the experimenter, which may limit the overall effectiveness of the Stepladder Technique. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ethical dilemmas in clinical supervision. 2: Need for guidelines

In this, the second half of this two-part article, the authors focus on ethical dilemmas in clinical supervision. Referring to the case vignettes included in the first part of this article (Vol 7(15): 920-3), the authors highlight how ethical dilemmas can arise and then provide some discussion on how they might be handled. As a result of the discussion, the authors conclude that there is a clear need for a specific set of guidelines to be produced that would help safeguard best practice within clinical supervision and ensure it remains an opportunity to help and support nurses in reflecting on their dilemmas, difficulties and successes (Cutcliffe and Proctor, 1998a). This would prevent supervision from becoming another form of management monitoring which might inadvertently prevent the resolution of intra- and interpersonal issues affecting the care of clients.     

A normative analytic framework for development of practice guidelines for specific clinical populations

BACKGROUND: A central problem in practice guideline development is how to develop guidelines that appropriately account for variations in clinical populations and practice settings. Despite recognition of this problem, there is no formal mechanism for assessing what the need is for flexibility in guidelines, or for deciding how to incorporate such flexibility into recommendations. OBJECTIVE: This research sought to provide a formal basis to determine when clinical circumstances vary sufficiently that guideline recommendations should differ, how recommendations should be tailored for a specific clinical setting, and whether the benefit associated with such site-specific guidelines justifies the expense of their development. RESULTS: The authors describe an approach for estimating the maximum health benefit that developers can obtain by eliminating uncertainty about differences in the patient populations and practice settings in which a guideline will be used. This estimate, the expected value of customization, provides a mechanism to evaluate the cost-effectiveness of the development of site-specific guidelines that account explicitly for variation in clinical circumstances. Application of this method to the development of screening guidelines for human immunodeficiency virus (HIV) infection indicates that the development of site-specific guidelines potentially is cost-effective. Site-specific guidelines either improve, or leave unchanged, the efficiency of HIV screening; whether they increase or decrease total expenditures and health benefits depends on the choice of a cost-effectiveness threshold, and the clinical problem. CONCLUSIONS: Development of guideline recommendations based on decision models provides a normative approach for evaluating the need for and the cost-effectiveness of site-specific guidelines that have been tailored to specific practice settings. Such site-specific guidelines can improve substantially the expected health benefit and the economic efficiency of practice guidelines.     

The challenges of clinical nursing research: strategies for successful conduct

Although the literature is replete with stringent methodological guidelines for designing experimental and quasi-experimental studies, there is a paucity of literature addressing the challenges of conducting these studies in the "real world" of the clinical setting. This article describes the challenges experienced by a team of researchers conducting a study in the acute care setting, including those associated with navigating organizational restructuring and managing within a climate of uncertainty. The study focused on the evaluation of a nurse-delivered smoking cessation intervention for hospitalized cardiac patients. As each particular challenge emerged, strategies were developed. By explicating these challenges and strategies, we hope to help clinical researchers deal with challenges proactively rather than reactively.     

A critical interpretation of Packer's "Hermeneutic inquiry in the study of human conduct."

Comments on the work of M. J. Packer (see record 1985-10720-001), focusing on 3 perceived flaws (Packer's interpretation of M. Heidegger's [1962] hermeneutic phenomenology; Packer's neglect of the role of language and linguistics in the subsequent development of hermeneutics; and his failure to locate his own version of hermeneutics among the types currently recognized and practiced). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modeling genetic and environmental influences in the etiology of conduct disorder: A study of 2,682 adult twin pairs.

The etiology of conduct disorder (CD) was examined retrospectively in a sample of 2,682 male, female, and unlike-sex adult twin pairs from the community-based Australian Twin Register. Model-fitting analyses indicated a substantial genetic influence on risk for CD, accounting for 71% of the variance (95% confidence interval [CI]?=?32–79%). There was not a statistically significant effect of the shared environment in the best-fitting model of CD, but a modest effect of the shared environment on the risk for CD could not be rejected (95% CI?=?0-32%). The magnitude of genetic and environmental influences for CD liability did not vary significantly for boys and girls, and the specific genetic and environmental mechanisms important for the development of CD appeared to be largely the same for both sexes. The fit of a multiple-threshold model raises the possibility that CD may not necessarily be a discrete entity but rather an extreme of the normal variation in conduct-disordered behavior found in the general population. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Multidimensionality of perceived locus of control: Two replications.

Administered Rotter's Internal-External Locus of Control Scale to 2 Australian samples, one of 159 14-19 yr old male adolescents and one of 134 18-20 yr old female adolescents. Both samples indicated the multidimensional structure of the scale in another culture, and pointed to the basic lack of relationship among its items. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Moral conduct and moral character: A psychological perspective.

Suggests that moral conduct can be explained and the development of moral character described in terms of 5 concepts or dimensions: moral knowledge, socialization, empathy, autonomy, and a dimension of moral judgment. These dimensions arise from a conception of man as a rule-formulating and rule-following animal and a view of morality as a methodology, a result of biological and cultural evolution, which regulates and moderates social conduct. Each concept is given a theoretical and an operational definition, its developmental antecedents are discussed, and evidence is provided concerning its usefulness as a means for understanding moral conduct. Finally, the model as a whole is evaluated. (52 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)