Activation of muscarinic acetylcholine receptors via their allosteric binding sites.

Ligands that bind to the allosteric-binding sites on muscarinic acetylcholine receptors alter the conformation of the classical-binding sites of these receptors and either diminish or increase their affinity for muscarinic agonists and classical antagonists. It is not known whether the resulting conformational change also affects the interaction between the receptors and the G proteins. We have now found that the muscarinic receptor allosteric modulators alcuronium, gallamine, and strychnine (acting in the absence of an agonist) alter the synthesis of cAMP in Chinese hamster ovary (CHO) cells expressing the M2 or the M4 subtype of muscarinic receptors in the same direction as the agonist carbachol. In addition, most of their effects on the production of inositol phosphates in CHO cells expressing the M1 or the M3 muscarinic receptor subtypes are also similar to (although much weaker than) those of carbachol. The agonist-like effects of the allosteric modulators are not observed in CHO cells that have not been transfected with the gene for any of the subtypes of muscarinic receptors. The effects of alcuronium on the formation of cAMP and inositol phosphates are not prevented by the classical muscarinic antagonist quinuclidinyl benzilate. These observations demonstrate for the first time that the G protein-mediated functional responses of muscarinic receptors can be evoked not only from their classical, but also from their allosteric, binding sites. This represents a new mechanism of receptor activation.     

Protocolized Laboratory Screening for the Medical Clearance of Psychiatric Patients in the Emergency Department: A Systematic Review

Objective

Emergency department (ED) patients with psychiatric chief complaints undergo medical screening to rule out underlying or comorbid medical illnesses prior to transfer to a psychiatric facility. This systematic review attempts to determine the clinical utility of protocolized laboratory screening for the streamlined medical clearance of ED psychiatric patients by determining the clinical significance of individual laboratory results.

Methods

We searched PubMed, Embase, and Scopus using the search terms “emergency department, psychiatry, diagnostic tests, laboratories, studies, testing, screening, and clearance” up to June 2017 for studies on adult psychiatric patients. This systematic review follows the recommendations of Meta‐analysis of Observational Studies in Epidemiology (MOOSE) statement. The quality of each study was rated according to the Newcastle‐Ottawa quality assessment scale.

Results

Four independent reviewers identified 2,847 publications. We extracted data from three studies (n = 629 patients). Included studies defined an abnormal test result as any laboratory result that falls out of the normal range. A laboratory test result was deemed as “clinically significant” only when patient disposition or treatment plan was changed because of that test result. Across the three studies the prevalence of clinically significant results were low (0.0%–0.4%).

Conclusions

The prevalence of clinically significant laboratory test results were low, suggesting that according to the available literature, routine laboratory testing does not significantly change patient disposition. Due to the paucity of available research on this subject, we could not determine the clinical utility of protocolized laboratory screening tests for medical clearance of psychiatric patients in the ED. Future research on the utility of routine laboratory testing is important in a move toward shared decision making and patient‐centered health care.

     

Improved Survival for Rural Trauma Patients Transported by Helicopter to a Verified Trauma Center: A Propensity Score Analysis

Objectives

Recent studies using advanced statistical methods to control for confounders have demonstrated an association between helicopter transport (HT) versus ground ambulance transport (GT) in terms of improved survival for adult trauma patients. The aim of this study was to apply a methodologically vigorous approach to determine if HT is associated with a survival benefit for when trauma patients are transported to a verified trauma center in a rural setting.

Methods

The ascertainment of trauma patients age ≥ 15 years (n = 469 cases) by HT and (n = 580 cases) by GT between 1999 and 2012 was restricted to the scene of injury in a rural area of 10 to 35 miles from the trauma center. The propensity score (PS) was determined using data including demographics, prehospital physiology, intubation, total prehospital time, and injury severity. The PS matching was performed with different calipers to select a higher percentage of matches of HT compared to GT patients. The outcome of interest was survival to discharge from hospital. Identical logistic regression analysis was done taking into account for each matched design to select an appropriate effect estimate and confidence interval (CI) controlling for initial vital signs in the emergency department, the need for urgent surgery, intensive care unit admission, and mechanical ventilation.

Results

Unadjusted mortalities for HT compared to GT were 7.7 and 5.3%, respectively (p > 0.05). The adjusted rates were 4.0% for HT and 7.6% for GT (p < 0.05). In a PS well‐matched data set, HT was associated with a 2.69‐fold increase in odds of survival compared to GT patients (adjusted odds ratio = 2.69; 95% CI = 1.21–5.97).

Conclusions

In a rural setting, we demonstrated improved survival associated with HT compared to GT for scene transportation of adult trauma patients to a verified Level II trauma center using an advanced methodologic approach, which included adjustment for transport distance. The implication of survival benefit to rural population is discussed. We recommend larger studies with multiple trauma systems need to be repeated using similar study methodology to substantiate our findings.     

Key High‐efficiency Practices of Emergency Department Providers: A Mixed‐methods Study

Objective

The objective of this study was to determine specific provider practices associated with high provider efficiency in community emergency departments (EDs).

Methods

A mixed‐methods study design was utilized to identify key behaviors associated with efficiency. Stage 1 was a convenience sample of 16 participants (ED medical directors, nurses, advanced practice providers, and physicians) identified provider efficiency behaviors during semistructured interviews. Ninety‐nine behaviors were identified and distilled by a group of three ED clinicians into 18 themes. Stage 2 was an observational study of 35 providers was performed in four (30,000‐ to 55,000‐visit) community EDs during two 4‐hour periods and recorded in minute‐by‐minute observation logs. In Stage 3, each behavior or practice from Stage 1 was assigned a score within each observation period. Behaviors were tested for association with provider efficiency (relative value units/hour) using linear univariate generalized estimating equations with an identity link, clustered on ED site.

Results

Five ED provider practices were found to be positively associated with efficiency: average patient load, using name of team member, conversations with health care team, visits to patient rooms, and running the board. Two behaviors, “inefficiency practices,” demonstrated significant negative correlations: non–work‐related tasks and documentation on patients no longer in the ED.

Conclusions

Average patient load, running the board, conversations with team member, and using names of team members are associated with enhanced provider productivity. Identification of behaviors associated with efficiency can be utilized by medical directors, clinicians, and trainees to improve personal efficiency or counsel team members.

     

Navigating systems ideas for health practice: Towards a common learning device

Systems thinking and reference to complexity science have gained currency in health sector practice and research. The extent to which such ideas might represent a mere passing fad or might more usefully be mobilized to tackle wicked problems in health systems is a concern underpinning this paper. Developing the usefulness of the systems idea requires appreciating how systems ideas are used essentially as constructs conceptually bounded by practitioners. Systems are used for purposes of understanding and engaging the reality of health issues, with the intent of transforming the reality into one that is more manageable, equitable, and sustainable. We examine some manifestations of the systems idea in health practice and the traditions of systems practice that variously make use of them. This provides a platform for proposing a systems thinking in (health) practice heuristic: a learning device supporting how different tools and methods can address “wicked problems” in health praxis. The device is built on the use of “conversation” as a metaphor to help practitioners use systems ideas in tandem with existing disciplinary and professional skills and methods. We consider how the application of the heuristic requires, and helps to develop, human characteristics of humility, empathy, and recognition of fallibility.