Guy R. Warman

Dexmedetomidine pharmacokinetics in pediatric intensive care--a pooled analysis.

Background:  Published dexmedetomidine pharmacokinetic studies in children are limited by participant numbers and restricted pathology. Pooling the available studies allows investigation of covariate effects.

Why does insect RNA look degraded

Abstract The integrity of extracted ribonucleic acid (RNA) is commonly assessed by gel electrophoresis and subsequent analysis of the ribosomal RNA (rRNA) bands. Using the honey bee, Apis mellifera (Hymenoptera: Apidae), as an example, the electrophoretic rRNA profile of insects is explained. This profile differs significantly from the standard benchmark since the 28S rRNA of most insects contains an endogenous “hidden break.” Upon denaturation, the masking hydrogen bonds are disrupted, releasing two similar sized fragments that both migrate closely with 18S rRNA. The resulting rRNA profile thus reflects the endogenous composition of insect rRNA and should not be misinterpreted as degradation.

Clonidine disposition in children; a population analysis.

Background:  There are few data describing clonidine population pharmacokinetics in children (0–15 years) despite common use. Current pediatric data, described in terms of elimination half‐life or Cmax and Tmax, poorly explain variability in drug responses among individuals representative of those in whom the drug will be used clinically.

Dexmedetomidine hemodynamics in children after cardiac surgery.

Background:  Dexmedetomidine has opposing effects on the cardiovascular system. Action in the central nervous system produces sympatholysis and a reduction in blood pressure, while peripherally it causes vasoconstriction leading to an increase in blood pressure. The purpose of our study is to define the concentration–response profile for these hemodynamic effects in children after cardiac surgery.

General anesthesia alters time perception by phase shifting the circadian clock

Following general anesthesia, people are often confused about the time of day and experience sleep disruption and fatigue. It has been hypothesized that these symptoms may be caused by general anesthesia affecting the circadian clock. The circadian clock is fundamental to our well-being because it regulates almost all aspects of our daily biochemistry, physiology, and behavior. Here, we investigated the effects of the most common general anesthetic, isoflurane, on time perception and the circadian clock using the honeybee (Apis mellifera) as a model. A 6-h daytime anesthetic systematically altered the time-compensated sun compass orientation of the bees, with a mean anticlockwise shift in vanishing bearing of 87° in the Southern Hemisphere and a clockwise shift in flight direction of 58° in the Northern Hemisphere. Using the same 6-h anesthetic treatment, time-trained bees showed a delay in the start of foraging of 3.3 h, and whole-hive locomotor-activity rhythms were delayed by an average of 4.3 h. We show that these effects are all attributable to a phase delay in the core molecular clockwork. mRNA oscillations of the central clock genes cryptochrome-m and period were delayed by 4.9 and 4.3 h, respectively. However, this effect is dependent on the time of day of administration, as is common for clock effects, and nighttime anesthesia did not shift the clock. Taken together, our results suggest that general anesthesia during the day causes a persistent and marked shift of the clock effectively inducing “jet lag” and causing impaired time perception. Managing this effect in humans is likely to help expedite postoperative recovery.

The impact of trained assistance on error rates in anaesthesia: a simulation‐based randomised controlled trial*

Trained assistance for the anaesthetist appears likely to improve safety in anaesthesia. However, there are few objective data to support this assumption, and the requirement for a trained assistant is not universally enforced. We applied a simulation‐based model developed in previous work to test the hypothesis that the presence of a trained assistant reduces error in anaesthesia. Ten randomly selected anaesthetists, five trained anaesthetic technicians and five theatre nurses without training in anaesthesia participated in two simulated emergencies, with anaesthetists working alternately with a technician or a nurse. The mean (SD) error rate per scenario was 4.75 (2.9). There were significantly fewer errors in the technician group than the nurse group (33 vs 62, p = 0.01) and this difference remained significant when errors were weighted for severity. This provides objective evidence supporting the requirement for trained assistance to the anaesthetist, and furthermore, demonstrates that a simulation‐based model can provide rigorous evidence on safety interventions in anaesthesia.

Way-finding in displaced clock-shifted bees proves bees use a cognitive map

Significance The question of the computational capacities of the brains of widely separated genera of animals is of interest to behavioral biologists, comparative psychologists, computational neuroscientists, philosophers of mind, and—we believe—much of the scientific community. Half a century ago, the claim that any nonhuman animal had a cognitive map was deeply controversial. If true, it greatly favored a computational theory of mind, as opposed to an antirepresentational behaviorist theory. Now that it is well established by behavioral and neurobiological evidence that rodents have a metric cognitive map, the question of whether insects do is a frontier question, the answer to which has broad implications in several disciplines. Mammals navigate by means of a metric cognitive map. Insects, most notably bees and ants, are also impressive navigators. The question whether they, too, have a metric cognitive map is important to cognitive science and neuroscience. Experimentally captured and displaced bees often depart from the release site in the compass direction they were bent on before their capture, even though this no longer heads them toward their goal. When they discover their error, however, the bees set off more or less directly toward their goal. This ability to orient toward a goal from an arbitrary point in the familiar environment is evidence that they have an integrated metric map of the experienced environment. We report a test of an alternative hypothesis, which is that all the bees have in memory is a collection of snapshots that enable them to recognize different landmarks and, associated with each such snapshot, a sun-compass–referenced home vector derived from dead reckoning done before and after previous visits to the landmark. We show that a large shift in the sun-compass rapidly induced by general anesthesia does not alter the accuracy or speed of the homeward-oriented flight made after the bees discover the error in their initial postrelease flight. This result rules out the sun-referenced home-vector hypothesis, further strengthening the now extensive evidence for a metric cognitive map in bees.

Prevalence of causes of insomnia in primary care: a cross-sectional study.

BACKGROUND As a result of a research interest in primary insomnia, the prevalence of other causes of insomnia in primary care must be ascertained. No source was found in the literature. It is also essential to know the epidemiology of the common causes of a condition to make an accurate diagnosis in primary care. AIM To determine the prevalence of causes of insomnia in primary care, as part of a method of identifying patients with primary insomnia. DESIGN AND SETTING Cross-sectional study in three general practices in Auckland, New Zealand. METHOD Consecutive patients from the waiting room were asked to complete a nine-page questionnaire on possible causes of insomnia. RESULTS In total, 1517 patients were approached and 955 completed the nine-page questionnaire (63%). Of the 41% (388) who reported difficulty with sleeping, primary insomnia occurred in 12% (45) of the population (95% confidence interval = 9% to 15%); 50% (195) had depression, 48% (185) had anxiety and 43% (165) had general (physical) health problems. Obstructive sleep apnoea occurred in 9% (34) and delayed sleep phase disorder in 2% (7). Only primary insomnia and delayed sleep phase disorder are mutually exclusive; the others can co-exist. CONCLUSION This is the first description of the prevalence of causes of insomnia in primary care. It is hoped that the focus on primary insomnia will result in more behavioural treatments and lower the use of hypnotics in primary care; it should also assist in the appropriate detection and treatment of other causes of insomnia in primary care.

Identifying advanced and delayed sleep phase disorders in the general population: a national survey of New Zealand adults.

The aim was to estimate the prevalence of, and identify independent risk factors for, Advanced (ASPD) and Delayed Sleep Phase Disorder (DSPD) among Māori (indigenous New Zealanders) and non-Māori adults using a self-report questionnaire. The Munich Chronotype Questionnaire was mailed to a stratified sample of 9100 adults (5100 Māori and 4000 non-Māori) aged 20–59 years randomly selected from the electoral rolls (54% response rate). Different definitions for ASPD and DSPD were developed using combinations of symptoms including self-reported bed and rising times, current chronotype, and a desire to change sleep schedule. Logistic regression models were used to model the likelihood of reporting ASPD or DSPD separately after adjusting for ethnicity (Māori versus non-Māori), sex (males versus females), age (in decades), socio-economic deprivation (NZDep2006 deciles) and employment status (unemployed, night work versus employed with no night work). The prevalence of ASPD ranged from 0.25% to 7.13% whereas the prevalence of DSPD was 1.51 to 8.90% depending on the definition used. The prevalence of ASPD was higher among men and increased with age. The prevalence of DSPD was higher among those living in more deprived areas and decreased with age. After controlling for ethnicity, gender, age, socio-economic deprivation and employment status, people with ASPD were more likely to report excessive daytime sleepiness, whereas those with DSPD were more likely to report poor or fair self-rated health. Reporting ASPD and DSPD were associated with self-reported night work. In this large sleep timing survey, we found no differences in the prevalence of self-identified ASPD and DSPD between Maori and non-Maori. This has implications for the development and provision of sleep health services and strategies for managing the significant impact of work patterns on sleep.

A simulation design for research evaluating safety innovations in anaesthesia

It is notoriously difficult to obtain evidence from clinical randomised controlled trials for safety innovations in healthcare. We have developed a research design using simulation for the evaluation of safety initiatives in anaesthesia. We used a standard and a modified scenario in a human‐patient simulator, involving a potentially life‐threatening problem requiring prompt attention – either a cardiac arrest or a failure in oxygen supply. The modified scenarios involved distractions such as loud music, a demanding and uncooperative surgeon, telephone calls and frequent questions from a medical student. Twenty anaesthetics were administered by 10 anaesthetists. A mean (SD) of 11.3 (2.8) errors per anaesthetic were identified in the oxygen failure scenarios, compared with 8.0 (3.4) in the cardiac arrest scenarios (ANOVA: p = 0.04). The difference between the combined standard scenarios and the combined modified scenarios was not significant. The mean rate of errors overall was 9.7 per simulation, with a pooled SD of 4.46, so in future studies 21 subjects would provide 80% statistical power to show a reduction in error rate of 30% from baseline with p≤0.05. Our research design will facilitate the evaluation of safety initiatives in anaesthesia.