Boolean Models of the Transport, Synthesis, and Metabolism of Tryptophan in Escherichia coli.

The tryptophan (trp) operon in Escherichia coli codes for the proteins responsible for the synthesis of the amino acid tryptophan from chorismic acid, and has been one of the most well-studied gene networks since its discovery in the 1960s. The tryptophanase (tna) operon codes for proteins needed to transport and metabolize it. Both of these have been modeled individually with delay differential equations under the assumption of mass-action kinetics. Recent work has provided strong evidence for bistable behavior of the tna operon. The authors of Orozco-Gómez et al. (Sci Rep 9(1):5451, 2019) identified a medium range of tryptophan in which the system has two stable steady-states, and they reproduced these experimentally. In this paper, we will show how a Boolean model can capture this bistability. We will also develop and analyze a Boolean model of the trp operon. Finally, we will combine these two to create a single Boolean model of the transport, synthesis, and metabolism of tryptophan. In this amalgamated model, the bistability disappears, presumably reflecting the ability of the trp operon to produce tryptophan and drive the system toward homeostasis. All of these models have longer attractors that we call "artifacts of synchrony", which disappear in the asynchronous automata. This curiously matches the behavior of a recent Boolean model of the arabinose operon in E. coli, and we discuss some open-ended questions that arise along these lines.

Phase I Trial of Anti-PSMA Designer CAR-T Cells in Prostate Cancer: Possible Role for Interacting Interleukin 2-T Cell Pharmacodynamics as a Determinant of Clinical Response.

BACKGROUND: Chimeric antigen receptor (CAR)-modified "designer" T cells (dTc, CAR-T) against PSMA selectively target antigen-expressing cells in vitro and eliminate tumors in vivo. Interleukin 2 (IL2), widely used in adoptive therapies, was proven essential in animal models for dTc to eradicate established solid tumors. METHODS: Patients under-went chemotherapy condi-tion-ing, followed by dTc dosing under a Phase I escalation with continuous infusion low dose IL2 (LDI). A target of dTc escalation was to achieve ≥20% engraftment of infused activated T cells. RESULTS: Six patients enrolled with doses prepared of whom five were treated. Patients received 10(9) or 10(10) autologous T cells, achieving expansions of 20-560-fold over 2 weeks and engraftments of 5-56%. Pharmacokinetic and pharmacodynamic analyses established the impact of conditioning to promote expansion and engraftment of the infused T cells. Unexpectedly, administered IL2 was depleted up to 20-fold with high engraftments of activated T cells (aTc) in an inverse correlation (P < 0.01). Clinically, no anti-PSMA toxicities were noted, and no anti-CAR reactivities were detected post-treatment. Two-of-five patients achieved clinical partial responses (PR), with PSA declines of 50% and 70% and PSA delays of 78 and 150 days, plus a minor response in a third patient. Responses were unrelated to dose size (P = 0.6), instead correlating inversely with engraftment (P = 0.06) and directly with plasma IL2 (P = 0.03), suggesting insufficient IL2 with our LDI protocol to support dTc anti-tumor activity under optimal (high) dTc engraftments. CONCLUSIONS: Under a Phase I dose escalation in prostate cancer, a 20% engraftment target was met or exceeded in three subjects with adequate safety, leading to study conclusion. Clinical responses were obtained but were suggested to be restrained by low plasma IL2 when depleted by high levels of engrafted activated T cells. This report presents a unique example of how the pharmaco-dynamics of "drug-drug" interactions may have a critical impact on the efficacy of their co-application. A new Pilot/Phase II trial is planned to test moderate dose IL2 (MDI) together with high dTc engraftments for anticipated improved therapeutic efficacy. Prostate 76:1257-1270, 2016. © 2016 Wiley Periodicals, Inc.

The synthesis of a series of adenosine A3 receptor agonists.

A series of 1'-(6-aminopurin-9-yl)-1'-deoxy-N-methyl-ß-d-ribofuranuronamides that were characterised by 2-dialkylamino-7-methyloxazolo[4,5-b]pyridin-5-ylmethyl substituents on N6 of interest for screening as selective adenosine A3 receptor agonists, have been synthesised. This work involved the synthesis of 2-dialkylamino-5-aminomethyl-7-methyloxazolo[4,5-b]pyridines and analogues that were coupled with the known 1'-(6-chloropurin-9-yl)-1'-deoxy-N-methyl-ß-d-ribofuranuronamide. The oxazolo[4,5-b]pyridines were synthesized by regioselective functionalisation of 2,4-dimethylpyridine N-oxides. The regioselectivities of these reactions were found to depend upon the nature of the heterocycle with 2-dimethylamino-5,7-dimethyloxazolo[4,5-b]pyridine-N-oxide undergoing regioselective functionalisation at the 7-methyl group on reaction with trifluoroacetic anhydride in contrast to the reaction of 4,6-dimethyl-3-hydroxypyridine-N-oxide with acetic anhydride that resulted in functionalisation of the 6-methyl group. To optimise selectivity for the A3 receptor, 5-aminomethyl-7-bromo-2-dimethylamino-4-[(3-methylisoxazol-5-yl)methoxy]benzo[d]oxazole was synthesised and coupled with the 1'-(6-chloropurin-9-yl)-1'-deoxy-N-methyl-ß-d-ribofuranuronamide. The products were active as selective adenosine A3 agonists.

Stereoselective synthesis of oxazolidinonyl-fused piperidines of interest as selective muscarinic (M1) receptor agonists: a novel M1 allosteric modulator.

Syntheses of (1RS,2SR,6SR)-2-alkoxymethyl-, 2-hetaryl-, and 2-(hetarylmethyl)-7-arylmethyl-4,7-diaza-9-oxabicyclo[4.3.0]nonan-8-ones, of interest as potential muscarinic M1 receptor agonists, are described. A key step in the synthesis of (1RS,2SR,6SR)-7-benzyl-6-cyclobutyl-2-methoxymethyl-4,7-diaza-9-oxabicyclo[4.3.0]nonan-8-one, was the addition of isopropenylmagnesium bromide to 2-benzyloxycarbonylamino-3-tert-butyldimethylsilyloxy-2-cyclobutylpropanal. This gave the 4-tert-butyldimethylsilyloxymethyl-4-cyclobutyl-5-isopropenyloxazolidinone with the 5-isopropenyl and 4-tert-butyldimethylsilyloxymethyl groups cis-disposed about the five-membered ring by chelation controlled addition and in situ cyclisation. This reaction was useful for a range of organometallic reagents. The hydroboration-oxidation of (4SR,5RS)-3-benzyl-4-(tert-butyldimethylsilyloxymethyl)-4-cyclobutyl-5-(1-methoxyprop-2-en-2-yl)-1,3-oxazolidin-2-one gave (4SR,5RS)-3-benzyl-4-(tert-butyldimethylsilyloxymethyl)-4-cyclobutyl-5-[(SR)-1-hydroxy-3-methoxyprop-2-yl]-1,3-oxazolidin-2-one stereoselectively. 4,7-Diaza-9-oxabicyclo[4.3.0]nonan-8-ones with substituents at C2 that could facilitate C2 deprotonation were unstable with respect to oxazolidinone ring-opening and this restricted both the synthetic approach and choice of 2-heteroaryl substituent. The bicyclic system with a 2-furyl substituent at C2 was therefore identified as an important target. The addition of 1-lithio-1-(2-furyl)ethene to 2-benzyloxycarbonylamino-3-tert-butyldimethylsilyloxy-2-cyclobutylpropanal gave (4SR,5RS)-4-tert-butyldimethylsilyloxymethyl-4-cyclobutyl-5-[1-(2-furyl)ethenyl]-1,3-oxazolidinone after chelation controlled addition and in situ cyclisation. Following oxazolidinone N-benzylation, hydroboration at 35 °C, since hydroboration at 0 °C was unexpectedly selective for the undesired isomer, followed by oxidation gave a mixture of side-chain epimeric alcohols that were separated after SEM-protection and selective desilylation. Conversion of the neopentylic alcohols into the corresponding primary amines by reductive amination, was followed by N-nosylation, removal of the SEM-groups and cyclisation using a Mitsunobu reaction. Denosylation then gave the 2-furyloxazolidinonyl-fused piperidines, the (1RS,2SR,6SR)-epimer showing an allosteric agonistic effect on M1 receptors. Further studies resulted in the synthesis of other 2-substituted 4,7-diaza-9-oxabicyclo[4.3.0]nonan-8-ones and an analogous tetrahydropyran.

The System-Wide Effect of Real-Time Audiovisual Feedback and Postevent Debriefing for In-Hospital Cardiac Arrest: The Cardiopulmonary Resuscitation Quality Improvement Initiative.

OBJECTIVE: To evaluate the effect of implementing real-time audiovisual feedback with and without postevent debriefing on survival and quality of cardiopulmonary resuscitation quality at in-hospital cardiac arrest. DESIGN: A two-phase, multicentre prospective cohort study. SETTING: Three UK hospitals, all part of one National Health Service Acute Trust. PATIENTS: One thousand three hundred and ninety-five adult patients who sustained an in-hospital cardiac arrest at the study hospitals and were treated by hospital emergency teams between November 2009 and May 2013. INTERVENTIONS: During phase 1, quality of cardiopulmonary resuscitation and patient outcomes were measured with no intervention implemented. During phase 2, staff at hospital 1 received real-time audiovisual feedback, whereas staff at hospital 2 received real-time audiovisual feedback supplemented by postevent debriefing. No intervention was implemented at hospital 3 during phase 2. MEASUREMENTS AND MAIN RESULTS: The primary outcome was return of spontaneous circulation. Secondary endpoints included other patient-focused outcomes, such as survival to hospital discharge, and process-focused outcomes, such as chest compression depth. Random-effect logistic and linear regression models, adjusted for baseline patient characteristics, were used to analyze the effect of the interventions on study outcomes. In comparison with no intervention, neither real-time audiovisual feedback (adjusted odds ratio, 0.62; 95% CI, 0.31-1.22; p=0.17) nor real-time audiovisual feedback supplemented by postevent debriefing (adjusted odds ratio, 0.65; 95% CI, 0.35-1.21; p=0.17) was associated with a statistically significant improvement in return of spontaneous circulation or any process-focused outcome. Despite this, there was evidence of a system-wide improvement in phase 2, leading to improvements in return of spontaneous circulation (adjusted odds ratio, 1.87; 95% CI, 1.06-3.30; p=0.03) and process-focused outcomes. CONCLUSIONS: Implementation of real-time audiovisual feedback with or without postevent debriefing did not lead to a measured improvement in patient or process-focused outcomes at individual hospital sites. However, there was an unexplained system-wide improvement in return of spontaneous circulation and process-focused outcomes during the second phase of the study.

Improving the efficiency of advanced life support training: a randomized, controlled trial.

BACKGROUND: Each year, more than 1.5 million health care professionals receive advanced life support (ALS) training. OBJECTIVE: To determine whether a blended approach to ALS training that includes electronic learning (e-learning) produces outcomes similar to those of conventional, instructor-led ALS training. DESIGN: Open-label, noninferiority, randomized trial. Randomization, stratified by site, was generated by Sealed Envelope (Sealed Envelope, London, United Kingdom). (International Standardized Randomized Controlled Trial Number Register: ISCRTN86380392) SETTING: 31 ALS centers in the United Kingdom and Australia. PARTICIPANTS: 3732 health care professionals recruited between December 2008 and October 2010. INTERVENTION: A 1-day course supplemented with e-learning versus a conventional 2-day course. MEASUREMENTS: The primary outcome was performance in a cardiac arrest simulation test at the end of the course. Secondary outcomes comprised knowledge- and skill-based assessments, repeated assessment after remediation training, and resource use. RESULTS: 440 of the 1843 participants randomly assigned to the blended course and 444 of the 1889 participants randomly assigned to conventional training did not attend the courses. Performance in the cardiac arrest simulation test after course attendance was lower in the electronic advanced life support (e-ALS) group compared with the conventional advanced life support (c-ALS) group; 1033 persons (74.5%) in the e-ALS group and 1146 persons (80.2%) in the c-ALS group passed (mean difference, -5.7% [95% CI, -8.8% to -2.7%]). Knowledge- and skill-based assessments were similar between groups, as was the final pass rate after remedial teaching, which was 94.2% in the e-ALS group and 96.7% in the c-ALS group (mean difference, -2.6% [CI, -4.1% to 1.2%]). Faculty, catering, and facility costs were $438 per participant for electronic ALS training and $935 for conventional ALS training. LIMITATIONS: Many professionals (24%) did not attend the courses. The effect on patient outcomes was not evaluated. CONCLUSION: Compared with conventional ALS training, an approach that included e-learning led to a slightly lower pass rate for cardiac arrest simulation tests, similar scores on a knowledge test, and reduced costs. PRIMARY FUNDING SOURCE: National Institute of Health Research and Resuscitation Council (UK).

Preventing Dental Caries: Part 1 the scientific rationale for preventive advice.

UNLABELLED: This article highlights the fundamental issues which the primary care team should consider when developing preventive dental advice for their patients. Although it is important to have a clear understanding of the carious process, this knowledge must take account of social influences on health when assessing the preventive strategy for individuals. A key factor is that caries is a lifelong process involving fluctuations in demineralization and remineralization. The dental team should ensure that the oral environment favours remineralization and avoids irreversible loss of enamel and dentine. An understanding of this'see-saw' process will influence not only our preventive philosophy but how we, as health professionals, diagnose and treat dental caries. CLINICAL RELEVANCE: Preventing dental caries is an essential skill for all dental professionals. This article brings together the scientific basis of the appropriate advice.

Preventing dental caries: part 2. Case studies in prevention.

UNLABELLED: This article seeks to bring together the preventive messages given in Paper 1 and apply them to specific individual patients. The key elements are the appropriate advice on fluorides, fissure sealants, diet and formulating advice in terms of an individual's educational background. CLINICAL RELEVANCE: This article offers practical advice on the prevention of dental caries using individual patient-based scenarios.

A Geospatial Analysis of Abortion Access in the United States After the Reversal of Roe v Wade.

OBJECTIVE: To investigate current abortion access in the United States based on geographic location and to forecast access according to the landscape of abortion care in the year after the Dobbs v Jackson Women's Health Organization decision. METHODS: Addresses of abortion-providing clinics were identified using web-based directories from Planned Parenthood, the National Abortion Foundation, Abortion Finder, and Power to Decide. Using geographic coordinates and the OpenStreetMap road network, Valhalla's Isochrone application programming interface was used to calculate the areas within a 30-, 60-, and 90-minute driving distance from these clinics. The population of reproductive-aged women (15-49 years) in the tracts inside or outside the accessible areas was determined using the U.S. Census American Community Survey for 2020. Review of legislative and judicial actions for 2023 determined at-risk states. Clinic locations and laws are accurate as of June 2, 2023. RESULTS: The addresses of 750 abortion facilities were geocoded. Currently, 41.4% (30.8 million) of women do not have access to an abortion clinic within a 30-minute drive, and 29.3% and 23.6% do not have access within a 60-minute and 90-minute drive, respectively. When accounting for the combined population with no access, severely limited access, and at-risk of losing access, 53.5% of women do not have access within a 30-minute drive, and 45.6% and 43.0% do not have access within a 60-minute and 90-minute drive, respectively. DISCUSSION: Two of every five American women do not have access to an abortion facility within a 30-minute drive, and one in four lack access within a 90-minute drive. These proportions could significantly increase if access is restricted further with state bans proposed in 2023.

Factors affecting team leadership skills and their relationship with quality of cardiopulmonary resuscitation.

OBJECTIVE: This study aims to explore the relationship between team-leadership skills and quality of cardiopulmonary resuscitation in an adult cardiac-arrest simulation. Factors affecting team-leadership skills were also assessed. DESIGN: Forty advanced life-support providers leading a cardiac arrest team in a standardized cardiac-arrest simulation were videotaped. Background data were collected, including age (in yrs), sex, whether they had received any leadership training in the past, whether they were part of a professional group, the most recent advanced life-support course (in months) they had undergone, advanced life-support instructor/provider status, and whether they had led in any cardiac arrest situation in the preceding 6 months. MEASUREMENTS AND MAIN RESULTS: Participants were scored using the Cardiac Arrest Simulation test score and Leadership Behavior Description Questionnaire for leadership skills. Process-focused quality of cardiopulmonary resuscitation data were collected directly from manikin and video recordings. Primary outcomes were complex technical skills (measured as Cardiac Arrest Simulation test score, preshock pause, and hands-off ratio). Secondary outcomes were simple technical skills (chest-compression rate, depth, and ventilation rate). Univariate linear regressions were performed to examine how leadership skills affect quality of cardiopulmonary resuscitation and bivariate correlations elicited factors affecting team-leadership skills.Teams led by leaders with the best leadership skills performed higher quality cardiopulmonary resuscitation with better technical performance (R = 0.75, p < .001), shorter preshock pauses (R = 0.18, p < .001), with lower total hands-off ratio (R = 0.24, p = .01), and shorter time to first shock (R = 0.14, p = .02). Leadership skills were not significantly associated with more simple technical skills such as chest-compression rate, depth, and ventilation rate. Prior training in team leader skills was independently associated with better leadership behavior. CONCLUSIONS: There is an association between team leadership skills and cardiac arrest simulation test score, preshock pause, and hands off ratio. Developing leadership skills should be considered an integral part of resuscitation training.

Dentifrices--an update.

OBJECTIVES: The objective of this paper was to review the published evidence concerning the efficacy and potential for adverse reactions of modern dentifrices toothpastes. DATA SOURCES: Publications cited on MEDLINE since 1990. Some further pre-1990 publications are also referenced. DATA SELECTION: Studies concerning the efficacy of dentifrices and their components and any related putative adverse incidents. DATA EXTRACTION: Papers were scrutinised for scientific and trial data. DATA SYNTHESIS: Data concerning the efficacy of dentifrice components were summarised. CONCLUSIONS: The efficacy of fluoride salts in dentifrices in reducing dental caries is well established. Toothpastes, containing triclosan, are effective in improving plaque control, gingivitis and periodontal health. Other toothpaste formulations are effective in reducing the formation of calculus, extrinsic tooth stain, dentine sensitivity and oral malodour. The consumer now has available a range of toothpastes which deliver oral health benefits. Adverse reactions to toothpastes are rare but should be considered in unexplained skin or respiratory allergies and gingival or lip lesions.

How effective are interdental cleaning aids in improving dental health?

UNLABELLED: This paper reviews recent systematic reviews of the evidence on the effectiveness of interdental cleaning aids in delivering oral health benefits. CLINICAL RELEVANCE: Dental professionals need to consider the evidence for the effectiveness of different interdental cleaning aids carefully when making recommendations to patients.

Advanced life support update.

INTRODUCTION: Cardiac arrest is a common emergency in acute hospitals. The Resuscitation Council (UK) Advanced Life Support Guidelines provide a systematic approach to cardiac arrest recognition, treatment and aftercare. This review provides an update on the current treatment guidelines and identifies areas where these may be strengthened. METHODS: The evidence informing the 2005 Resuscitation Guidelines is reviewed. New evidence since the publication of the guidelines was identified by searching Medline (December 2005-December 2008) with the term heart arrest or advanced life support. RESULTS: Opportunities for strengthening the chain of survival exist for each link. These include better recognition of critically ill patients at risk of cardiac arrest, improved quality of cardiopulmonary resuscitation, defibrillation strategies, which minimize pre- and post-shock pauses and development of post-resuscitation care bundles. CONCLUSION: Emerging evidence suggests opportunities where Resuscitation Guidelines could be strengthened by focusing on specific aspects of the chain of survival.

Compression feedback devices over estimate chest compression depth when performed on a bed.

INTRODUCTION: CPR feedback/prompt devices are being used increasingly to guide CPR performance in clinical practice. A potential limitation of these devices is that they may fail to measure the amount of mattress compression when CPR is performed on a bed. The aim of this study is to quantify the amount of mattress compression compared to chest compression using a commercially available compression sensor (Q-CPR, Laerdal, UK). A secondary aim was to evaluate if placing a backboard beneath the victim would alter the degree of mattress compression. METHODS: CPR was performed on a manikin on the floor and on a bed with a foam or inflatable mattress with and without a backboard. Chest and mattress compression depths were measured by an accelerometer placed on the manikin's chest (total compression depth) and sternal-spinal (chest) compression by manikin sensors. RESULTS: Feedback provided by the accelerometer device led to significant under compression of the chest when CPR was performed on a bed with a foam 26.2 (2.2)mm or inflatable mattress 32.2 (1.16)mm. The use of a narrow backboard increased chest compression depth by 1.9mm (95% CI 0.1-3.7mm; P=0.03) and wide backboard by 2.6mm (95% CI 0.9-4.5mm; P=0.013). Under compression occurred as the device failed to compensate for compression of the underlying mattress, which represented 35-40% of total compression depth. CONCLUSION: The use of CPR feedback devices that do not correct for compression of an underlying mattress may lead to significant under compression of the chest during CPR.

The application of fluoride varnish in the prevention and control of dental caries.

UNLABELLED: The method of applying fluoride varnish is described and the evidence of its effectiveness in the prevention and control of caries is summarized.The application of fluoride varnish should be an integral part of caries preventive programmes. CLINICAL RELEVANCE: This paper describes how to apply fluoride varnish and reviews its effectiveness in preventing caries.

Quality of CPR during advanced resuscitation training.

INTRODUCTION: Previous studies have documented poor quality CPR during real life resuscitation attempts. This study investigated whether poor quality CPR during advanced life support training could be contributing to poor performance in clinical practice. METHODS: Observational study of quality of CPR during advanced life support training courses before and after the implementation of the European Resuscitation Council Guidelines 2005 into the ALS course. The quality of chest compressions were downloaded from a manikin and direct observations of no-flow time; pre-shock pauses were recorded. RESULTS: 94 cardiac arrest simulations were studied (46 before implementation of Guidelines 2005 and 48 after). Delays in starting CPR, inadequate compression depth, prolonged interruptions of chest compressions and excessive pre-shock pauses were identified. The introduction of Guidelines 2005 resulted in improvements in the number of compressions given per minute and a reduction in no-flow time and duration of pre-shock pauses, but overall the quality of CPR performed during the ALS course remained poor. There was little evidence of performance improving over successive simulations as the course progressed. CONCLUSION: The implementation of Guidelines 2005 into the ALS course appear to have improved the process of CPR by reducing no-flow time during simulated CPR. However, the quality of CPR during ALS training remains sub-optimal. Delays in starting CPR, inadequate compression depth, excessive interruptions in chest compressions and prolonged pre-shock pauses mirror observations from clinical practice. Strategies to improve CPR performance during ALS training should be explored and potentially may result in improvements in clinical practice.

Delivering better oral health--an evidence-based toolkit for prevention: a review.

UNLABELLED: This article aims to give background to the UK's Department of Health evidence-based prevention toolkit for clinical teams. Initially, it describes the purpose, principles and format of the toolkit and then lists some of the key preventive messages contained within it. Finally, the factors which may affect its impact on dental health are discussed. CLINICAL RELEVANCE: Clinical teams will find the evidence-based prevention toolkit helpful when implementing a preventive approach.

High fluoride toothpastes: their potential role in a caries prevention programme.

UNLABELLED: This paper reviews the clinical evidence for the effectiveness of two, prescription only, toothpastes which contain 2800 and 5000 ppm F. The potential benefit of these toothpastes for high caries risk adolescents, adults and the elderly are discussed. CLINICAL RELEVANCE: Dentists are now able to prescribe two high fluoride toothpastes for high caries risk individuals.

The impact of manual defibrillation technique on no-flow time during simulated cardiopulmonary resuscitation.

INTRODUCTION: Rapid defibrillation is the most effective strategy for establishing return of spontaneous circulation following cardiac arrest due to ventricular fibrillation. The aim of this study is to measure the delay due to of charging the defibrillator during chest compression in an attempt to reduce the duration of the pre-shock pause in between cessation of chest compressions and shock delivery as advocated by the American Heart Association (AHA) guidelines compared to charging the defibrillator immediately following rhythm analysis without resuming chest compressions as recommended by the European Resuscitation Council (ERC). METHODS: This was a randomised controlled cross over trial comparing pre-shock pause times when defibrillation was performed on a manikin according to the AHA and ERC guidelines using paddles and hands free defibrillation systems. RESULTS: The pre-shock pause between cessation of chest compression and shock delivery was significantly different between techniques (Friedman test, P<0.0001). ERC paddles technique had the greatest pre-shock pause (7.4 s [6.7-11.2]) followed by ERC hands free (7.0 s [6.5-8.5]) and AHA paddles (1.6 s [1.1-2.3]). AHA hands free took the least amount of time (1.5 s [0.8-1.5]). Extrapolating these data to older defibrillators with longer charge times saw pre-shock pause intervals of 9 s (Codemaster XL) and 12 s (Lifepak 20) with the ERC approach. CONCLUSION: This study demonstrated clinically significant delays to defibrillation by analysing and charging the defibrillator without performing concurrent chest compressions. In a simulated scenario, charging the defibrillator whilst performing chest compressions was perceived as safe and significantly reduced the pre-shock pause between cessation of chest compression and shock delivery.

Advanced life support cardiac arrest scenario test evaluation.

BACKGROUND: The cardiac arrest scenario test (CASTest) is a central component of the assessment strategy on the Advanced Life Support Course. The aim of this study was to establish equivalence between the four different CASTest scenarios and investigate the impact of profession, candidate order and course centre on the pass rate. MATERIALS AND METHODS: This was a cluster randomised study. CASTest scenarios were randomly allocated to candidates stratified by course centre. Candidate demographics and performance were recorded on the criterion referenced check list along with the final assessment outcome (pass/fail). Differences in pass rates according scenario; profession, course centre and candidate order were examined by Chi-squared and multiple logistic regression. RESULTS: Two thousand, four hundred and forty-nine assessments from 65 course centres were evaluated. There was no difference in pass rate between scenarios (average pass rate 74.4%). Pass rates according to course centre varied widely (40-93%, P<0.0001) as did professional group (42-100%, P<0.0001). The order that candidates took the test did not influence the pass rate. CONCLUSION: The CASTest assessment scenarios used during ALS testing appear equivalent in terms of difficulty. In contrast, the professional background of the candidate and centre at which the assessment is performed do significantly influence the likelihood of passing the assessment. Further evaluation of the reasons for differences between course centres is required.