Evolution of Dihydropyrimidine Dehydrogenase Diagnostic Testing in a Single Center during an 8-Year Period of Time.

OBJECTIVE: Fluoropyrimidine treatment can be optimized based on dihydropyrimidine dehydrogenase (DPD) activity. DPD dysfunction leads to increased exposure to active metabolites, which can result in severe or even fatal toxicity. METHODS: We provide an overview of 8 years of DPD diagnostic testing (n = 1194). RESULTS: Within the study period, our diagnostic test evolved from a single-enzyme measurement using first a radiochemical and then a nonradiochemical assay by ultra HPLC-MS in peripheral blood mononuclear cells with uracil, to a combined enzymatic and genetic test (ie, polymerase chain reaction) followed by Sanger sequence analysis of 4 variants of the DPYD gene (ie, DPYD*2A, DPYD*13, c.2846A>T, and 1129-5923C>G; allele frequencies 0.58%, 0.03%, 0.29%, and 1.35%, respectively). Patients who have 1 of the 4 variants tested (n = 814) have lower enzyme activity than the overall patient group. The majority of patients with the DPYD*2A variant (83%) consistently showed decreased enzyme activity. Only 24 (25.3%) of 95 patients (tested for 4 variants) with low enzyme activity carried a variant. Complete DPYD sequencing in a subgroup with low enzyme activity and without DPYD*2A variant (n = 47) revealed 10 genetic variants, of which 4 have not been described previously. We did not observe a strong link between DPYD genotype and enzyme activity. CONCLUSIONS: Previous studies have shown that DPD status should be determined before treatment with fluoropyrimidine agents to prevent unnecessary side effects with possible fatal consequences. Our study in combination with literature shows that there is a discrepancy between the DPD enzyme activity and the presence of clinically relevant single nucleotide polymorphisms. At this moment, a combination of a genetic and enzyme test is preferable for diagnostic testing. (Curr Ther Res Clin Exp. 2018; 79:XXX-XXX).

Hands-on time during cardiopulmonary resuscitation is affected by the process of teambuilding: a prospective randomised simulator-based trial.

BACKGROUND: Cardiac arrests are handled by teams rather than by individual health-care workers. Recent investigations demonstrate that adherence to CPR guidelines can be less than optimal, that deviations from treatment algorithms are associated with lower survival rates, and that deficits in performance are associated with shortcomings in the process of team-building. The aim of this study was to explore and quantify the effects of ad-hoc team-building on the adherence to the algorithms of CPR among two types of physicians that play an important role as first responders during CPR: general practitioners and hospital physicians. METHODS: To unmask team-building this prospective randomised study compared the performance of preformed teams, i.e. teams that had undergone their process of team-building prior to the onset of a cardiac arrest, with that of teams that had to form ad-hoc during the cardiac arrest. 50 teams consisting of three general practitioners each and 50 teams consisting of three hospital physicians each, were randomised to two different versions of a simulated witnessed cardiac arrest: the arrest occurred either in the presence of only one physician while the remaining two physicians were summoned to help ("ad-hoc"), or it occurred in the presence of all three physicians ("preformed"). All scenarios were videotaped and performance was analysed post-hoc by two independent observers. RESULTS: Compared to preformed teams, ad-hoc forming teams had less hands-on time during the first 180 seconds of the arrest (93 +/- 37 vs. 124 +/- 33 sec, P < 0.0001), delayed their first defibrillation (67 +/- 42 vs. 107 +/- 46 sec, P < 0.0001), and made less leadership statements (15 +/- 5 vs. 21 +/- 6, P < 0.0001). CONCLUSION: Hands-on time and time to defibrillation, two performance markers of CPR with a proven relevance for medical outcome, are negatively affected by shortcomings in the process of ad-hoc team-building and particularly deficits in leadership. Team-building has thus to be regarded as an additional task imposed on teams forming ad-hoc during CPR. All physicians should be aware that early structuring of the own team is a prerequisite for timely and effective execution of CPR.

How accurate is information transmitted to medical professionals joining a medical emergency? A simulator study.

OBJECTIVE: This study used a high-fidelity simulation to examine factors influencing the accuracy of 201 pieces of information transmitted to nurses and physicians joining a medical emergency situation. BACKGROUND: Inaccurate or incomplete information transmission has been identified as a major problem in medicine. However, only a few studies have assessed possible causes of transmission errors. METHOD: Each of 20 groups was composed of two or three nurses (first responders), one resident joining the group later, and one senior doctor joining last. Groups treated a patient suffering a cardiac arrest. RESULTS: Multilevel binomial analyses showed that 18% of the information given to newcomers was inaccurate. Quantitative information requiring repeated updating was particularly error prone. Information generated earlier (i.e., older information) was more likely to be transmitted inaccurately. Explicitly encoding information to be transmitted after the physicians arrived at the scene enhanced accuracy, supporting transfer-appropriate processing theory. CONCLUSION: Information transmitted to nurses and physicians who join an ongoing emergency is only partly reliable. Therefore, medical professionals should not take accuracy for granted and should be aware of the nature of transmission errors. APPLICATION: Medical professionals should be trained in adequate encoding of information and in standardized communication procedures with regard to error-prone information. In addition, technical devices should be implemented that reduce reliance on memory regarding information with error-prone characteristics.

Performance of first responders in simulated cardiac arrests.

OBJECTIVE: Survival of in-hospital cardiac arrests depends more on first responders than on cardiac arrest teams. The objective of this study was to determine the adherence to algorithms of cardiopulmonary resuscitation of first responders in simulated cardiac arrests in intensive care. A second objective was to assess the effect of the early vs. late availability of a physician on the performance of nurse-based teams acting as first responders. DESIGN: Prospective study. SETTING: Patient simulator in a tertiary level intensive care unit. PARTICIPANTS: A total of 20 teams consisting of three registered nurses and one resident each. INTERVENTIONS: A simulated witnessed cardiac arrest due to ventricular fibrillation occurred in the presence of one nurse while the remaining two nurses could be called to help. Depending on the time of the residents' arrival, teams were classified as "early" (median arrival 50 secs after the onset of the arrest) or "late" (median arrival 150 secs after the onset of the arrest). MEASUREMENTS AND MAIN RESULTS: In all teams, the recognition of the arrest and the calling for help occurred in a timely fashion. However, a median of 85 secs (interquartile range [IQ], 130 secs) elapsed until the start of cardiac massage and 100 secs (IQ, 45 secs) to the first defibrillation. Once commenced, cardiac massage and mask ventilation were carried out during 61% (IQ, 33%) and 77% (IQ, 23%) of the possible time only. Delays and interruptions were generally not recalled by the participants. Compared with teams with late arriving residents, teams with early arriving residents administered more countershocks: 4.5 (IQ, 2) vs. 3.5 (IQ, 1.5; p = .026). CONCLUSIONS: First responders in intensive care often failed to build a team structure that ensured timely, effective, monitored, and ongoing team activity. The early availability of a physician increased the number of countershocks administered. Self-reporting is unsuitable to reliably assess the quality of cardiopulmonary resuscitation.