Carl-Oscar Jonson

The association of CTLA-4 and HLA class II autoimmune risk genotype with regulatory T cell marker expression in 5-year-old children

Regulatory T cells (Treg) are involved in the maintenance of peripheral tolerance by suppression of autoreactive lymphocytes that have avoided thymic depletion. The defective function of Treg cells has recently attracted attention in autoimmune diseases such as type 1 diabetes (T1D), rheumatoid arthritis and multiple sclerosis. Susceptibility to these diseases is associated with specific human leucocyte antigen (HLA) class II and cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4) gene polymorphisms. This study aimed to investigate the relationship between HLA class II and CTLA +49 A/G polymorphisms associated with susceptibility to T1D and the number and characteristics of Treg cells in children. Samples from 47 5‐year‐old children who participated in the All Babies in South‐east Sweden (ABIS) follow‐up study were grouped according to the presence of the T1D risk‐associated HLA genotype (DQA1*0501–DQB1*0201, DQA1*0301–DQB1*0302) or neutral HLA genotypes. Lower percentages of CD4+ T cells (P = 0·03) and CD4+ CD25high cells (P = 0·06) expressing intracellular CTLA‐4 were detected in samples from children with CTLA‐4 +49GG compared to children with the +49AA genotype. Similarly, lower percentages of CD4+ (P = 0·002) and CD4+ CD25high (P = 0·002) cells expressing CTLA‐4 were observed in children positive for HLA DQA1*0501–DQB1*0201 and DQA1*0301–DQB1*0302 (P = 0·04 for CD4+ and P = 0·02 for CD4+ CD25high) risk haplotypes when compared to children without these alleles. The percentage of CD25high cells among CD4+ cells was correlated inversely with CTLA‐4 mRNA expression in PBMC (r = –0·56, P = 0·03). Decreased levels of CTLA‐4 in CD4+ and CD4+ CD25high cells in individuals with CTLA‐4 and HLA class II alleles associated with T1D may contribute to the initiation and/or progression of autoimmune response.

The importance of CTLA‐4 polymorphism and human leukocyte antigen genotype for the induction of diabetes‐associated cytokine response in healthy school children

Background:  Type 1 diabetes (T1D) is an autoimmune disease associated with the destruction of pancreatic β cells and genetically linked to human leukocyte antigen (HLA) class II DR3‐DQ2 and DR4‐DQ8 haplotypes. The +49A/G polymorphism of the immunoregulatory cytotoxic T‐lymphocyte antigen 4 (CTLA‐4) gene is also associated with T1D. Genetic and environmental risk factors precede the onset of T1D, which is characterized by a T helper 1 cell‐dominating cytokine response to diabetes‐related autoantigens.

Performance indicators for initial regional medical response to major incidents: a possible quality control tool

BackgroundTimely decisions concerning mobilization and allocation of resources and distribution of casualties are crucial in medical management of major incidents. The aim of this study was to evaluate documented initial regional medical responses to major incidents by applying a set of 11 measurable performance indicators for regional medical command and control and test the feasibility of the indicators.MethodsRetrospective data were collected from documentation from regional medical command and control at major incidents that occurred in two Swedish County Councils. Each incident was assigned to one of nine different categories and 11 measurable performance indicators for initial regional medical command and control were systematically applied. Two-way analysis of variance with one observation per cell was used for statistical analysis and the post hoc Tukey test was used for pairwise comparisons.ResultsThe set of indicators for regional medical command and control could be applied in 102 of the130 major incidents (78%), but 36 incidents had to be excluded due to incomplete documentation. The indicators were not applicable as a set for 28 incidents (21.5%) due to different characteristics and time frames. Based on the indicators studied in 66 major incidents, the results demonstrate that the regional medical management performed according to the standard in the early phases (1–10 min after alert), but there were weaknesses in the secondary phase (10–30 min after alert). The significantly lowest scores were found for Indicator 8 (formulate general guidelines for response) and Indicator 10 (decide whether or not resources in own organization are adequate).ConclusionsMeasurable performance indicators for regional medical command and control can be applied to incidents that directly or indirectly involve casualties provided there is sufficient documentation available. Measurable performance indicators can enhance follow- up and be used as a structured quality control tool as well as constitute measurable parts of a nationally based follow-up system for major incidents. Additional indicators need to be developed for hospital-related incidents such as interference with hospital infrastructure.

Studying distributed cognition of simulation-based team training with DiCoT

Abstract Health care organizations employ simulation-based team training (SBTT) to improve skill, communication and coordination in a broad range of critical care contexts. Quantitative approaches, such as team performance measurements, are predominantly used to measure SBTTs effectiveness. However, a practical evaluation method that examines how this approach supports cognition and teamwork is missing. We have applied Distributed Cognition for Teamwork (DiCoT), a method for analysing cognition and collaboration aspects of work settings, with the purpose of assessing the methodology’s usefulness for evaluating SBTTs. In a case study, we observed and analysed four Emergo Train System® simulation exercises where medical professionals trained emergency response routines. The study suggests that DiCoT is an applicable and learnable tool for determining key distributed cognition attributes of SBTTs that are of importance for the simulation validity of training environments. Moreover, we discuss and exemplify how DiCoT supports design of SBTTs with a focus on transfer and validity characteristics. Practitioner Summary: In this study, we have evaluated a method to assess simulation-based team training environments from a cognitive ergonomics perspective. Using a case study, we analysed Distributed Cognition for Teamwork (DiCoT) by applying it to the Emergo Train System®. We conclude that DiCoT is useful for SBTT evaluation and simulator (re)design.

Low expression and secretion of circulating soluble CTLA-4 in peripheral blood mononuclear cells and sera from type 1 diabetic children

High levels of soluble cytotoxic T‐lymphocyte antigen 4 (soluble CTLA‐4), an alternative splice form of the regulatory T‐cell (Treg) associated CTLA‐4 gene, have been associated with type 1 diabetes (T1D) and other autoimmune diseases, such as Graves disease and myasthenia gravis. At the same time, studies have shown soluble CTLA‐4 to inhibit T‐cell activation through B7 binding. This study aimed to investigate the role of soluble CTLA‐4 in relation to full‐length CTLA‐4 and other Treg‐associated markers in T1D children and in individuals with high or low risk of developing the disease.

Simulation-assisted burn disaster planning

The aim of the study was to evaluate the Swedish medical systems response to a mass casualty burn incident in a rural area with a focus on national coordination of burn care. Data were collected from two simulations of a mass casualty incident with burns in a rural area in the mid portion of Sweden close to the Norwegian border, based on a large inventory of emergency resources available in this area as well as regional hospitals, university hospitals and burn centres in Sweden and abroad. The simulation system Emergo Train System(®) (ETS) was used and risk for preventable death and complications were used as outcome measures: simulation I, 18.5% (n=13) preventable deaths and 15.5% (n=11) preventable complications; simulation II, 11.4% (n=8) preventable deaths and 11.4% (n=8) preventable complications. The last T1 patient was evacuated after 7h in simulation I, compared with 5h in simulation II. Better national coordination of burn care and more timely distribution based on the experience from the first simulation, and possibly a learning effect, led to a better patient outcome in simulation II. The experience using a system that combines both process and outcome indicators can create important results that may support disaster planning.

Triage performance of Swedish physicians using the ATLS algorithm in a simulated mass casualty incident : a prospective cross-sectional survey

BackgroundIn a mass casualty situation, medical personnel must rapidly assess and prioritize patients for treatment and transport. Triage is an important tool for medical management in disaster situations. Lack of common international and Swedish triage guidelines could lead to confusion. Attending the Advanced Trauma Life Support (ATLS) provider course is becoming compulsory in the northern part of Europe. The aim of the ATLS guidelines is provision of effective management of single critically injured patients, not mass casualties incidents. However, the use of the ABCDE algorithms from ATLS, has been proposed to be valuable, even in a disaster environment. The objective for this study was to determine whether the mnemonic ABCDE as instructed in the ATLS provider course, affects the ability of Swedish physician’s to correctly triage patients in a simulated mass casualty incident.MethodsThe study group included 169 ATLS provider students from 10 courses and course sites in Sweden; 153 students filled in an anonymous test just before the course and just after the course. The tests contained 3 questions based on overall priority. The assignment was to triage 15 hypothetical patients who had been involved in a bus crash. Triage was performed according to the ABCDE algorithm. In the triage, the ATLS students used a colour-coded algorithm with red for priority 1, yellow for priority 2, green for priority 3 and black for dead. The students were instructed to identify and prioritize 3 of the most critically injured patients, who should be the first to leave the scene. The same test was used before and after the course.ResultsThe triage section of the test was completed by 142 of the 169 participants both before and after the course. The results indicate that there was no significant difference in triage knowledge among Swedish physicians who attended the ATLS provider course. The results also showed that Swedish physicians have little experience of real mass casualty incidents and exercises.ConclusionThe mnemonic ABCDE doesn’t significantly affect the ability of triage among Swedish physicians. Actions to increase Swedish physicians’ knowledge of triage, within the ATLS context or separately, are warranted.

Designing a Digital Medical Management Training Simulator Using Distributed Cognition Theory

Background. Training of medical professionals is important to improve care during mass-causality events. Therefore, it is essential to extend knowledge on how to design valid and usable simulation-based training environments. Purpose. This article investigates how distributed cognition and simulation theory concepts can guide design of simulation-based training environments. We present the design and user evaluation of DigEmergo, a simulator for training and assessing emergency medicine management. Design approach. A prior Distributed Cognition in Teamwork (DiCoT) analysis of the Emergo Train System (ETS) guided the design process. The design objective of DigEmergo was to be useful, usable, retain distributed cognition features of ETS, and strengthen validity and output reliability. Evaluation. Eight expert ETS instructors participated in a formative system evaluation. The Technology Assessment Model (TAM) questionnaire was used to measure usefulness and ease of use. Observations and post-test interviews were conducted to contextualize the measures. Results. The results showed that DigEmergo was perceived as somewhat to quite useful and somewhat easy to use. Overall, expert users considered DigEmergo promising and successful in retaining core ETS features. Conclusions. The study indicates that a design methodology based on distributed cognition and simulation theory can be successfully combined to guide simulator (re)design and strengthen simulator validity.

Exploring prehospital C2-work during a mass gathering event

Purpose– The purpose of this paper is to explore the workload and shared workload awareness in a staff performing command and control (C2) work during a planned major incident (MI) empirical case in Sweden. Design/methodology/approach– Data on workload and shared awareness were collected during live C2-work using qualitative observations and in-situ interviews mixed with quantitative questionnaires. Findings– A content analysis of the qualitative data revealed categories of workload sources. Quantified workload estimates showed changes in workload levels over time and staff roles, which were also contextualized using the results of the qualitative data. Data on shared awareness indicated that team workload awareness shifted over time according to common patterns. This study demonstrates a promising methodology to study C2-related factors during live EMS work. Research limitations/implications– The observed variations in workload imply that research that relies only on post-task measurements of workload may be inaccurate. Future research could use this method to investigate the connection between workload and performance during different types of MIs. Originality/value– The results can be used to inform future Goteborgsvarvet C2-teams in terms of when, why, and for whom task load changes, which would support predictive allocation of resources.

Pre-hospital triage performance after standardized trauma courses

BackgroundThe pre-hospital triage process aims at identifying and prioritizing patients in the need of prompt intervention and/or evacuation. The objective of the present study was to evaluate triage decision skills in a Mass Casualty Incident drill. The study compares two groups of participants in Advanced Trauma Life Support and Pre-Hospital Trauma Life Support courses.MethodsA questionnaire was used to deal with three components of triage of victims in a Mass Casualty Incident: decision-making; prioritization of 15 hypothetical casualties involved in a bus crash; and prioritization for evacuation. Swedish Advanced Trauma Life Support and Pre-Hospital Trauma Life Support course participants filled in the same triage skills questionnaire just before and after their respective course.ResultsOne hundred fifty-three advanced Trauma Life Support course participants were compared to 175 Pre-Hospital Trauma Life Support course participants. The response rates were 90% and 95%, respectively. A significant improvement was found between pre-test and post-test for the Pre-Hospital Trauma Life Support group in regards to decision-making. This difference was only noticeable among the participants who had previously participated in Mass Casualty Incident drills or had experience of a real event (pre-test mean ± standard deviation 2.4 ± 0.68, post-test mean ± standard deviation 2.60 ± 0.59, P = 0.04). No improvement was found between pre-test and post-test for either group regarding prioritization of the bus crash casualties or the correct identification of the most injured patients for immediate evacuation.ConclusionsNeither Advanced Trauma Life Support nor Pre-Hospital Trauma Life Support participants showed general improvement in their tested triage skills. However, participation in Mass Casualty Incident drills or experience of real events prior to the test performed here, were shown to be advantageous for Pre-Hospital Trauma Life Support participants. These courses should be modified in order to assure proper training in triage skills.