The importance of non-technical performance for teams managing postpartum haemorrhage: video review of 99 obstetric teams.

OBJECTIVE: Little is known about how teams' non-technical performance influences clinical performance in obstetric emergencies such as postpartum haemorrhage. DESIGN: Video review - observational study. SETTING: A university hospital (5000 deliveries) and a regional hospital (2000 deliveries) in Denmark. POPULATION: Obstetric teams managing real-life postpartum haemorrhage. METHODS: We systematically assessed 99 video recordings of obstetric teams managing real-life major postpartum haemorrhage. Exposure was the non-technical score (AOTP); outcomes were the clinical performance score (TeamOBS) and the delayed transfer to the operating theatre (defined as blood loss >1500 ml in the delivery room). RESULTS: Teams with an excellent non-technical score performed significantly better than teams with a poor non-technical score: 83.7 versus 0.3% chance of a high clinical performance score (P < 0.001), 0.2 versus 80% risk of a low clinical performance score (P < 0.001), and 3.5 versus 31.7% risk of delayed transfer to the operating theatre (P = 0.008). The results remained robust when adjusting for potential confounders such as bleeding velocity, aetiology, time of day, team size, and hospital. The specific non-technical skills associated with high clinical performance were vigilance, role assignment, problem-solving, management of disruptive behavior, and leadership. Communication with the patient and closing the loop were of minor importance. All performance assessments showed good reliability: the intraclass correlation was 0.97 (95% CI 0.96-0.98) for the non-technical score and 0.84 (95% CI 0.76-0.89) for the clinical performance score. CONCLUSION: Video review offers a new method and new perspectives for research in obstetric teams to identify how teams become effective and safe; the skills identified in this study can be included in future obstetric training programmes. TWEETABLE ABSTRACT: Non-technical performance is important for teams managing postpartum haemorrhage; video review of 99 obstetric teams.

Cross-sectional increase of adherence to multidisciplinary tumor board decisions.

BACKGROUND: Cancer research has made great progress in the recent years. With the increasing number of options in diagnosis and therapy the implementation of tumorboards (TUBs) has become standard procedure in the treatment of cancer patients. Adherence tests on tumor board decisions are intended to enable quality assurance and enhancement for work in tumor boards in order to continuously optimize treatment options for cancer patients. METHODS: Subject of this study was the adherence of the recommendations made in three of 14 tumorboards, which take place weekly in the Center for Integrated Oncology (CIO) at the University Hospital Bonn. In total, therapy recommendations of 3815 patient cases were checked on their implementation. A classification into four groups has been made according to the degree of implementation. A second classification followed regarding the reasons for differences between the recommendation and the therapy which the patient actually received. RESULTS: The study showed that 80.1% of all recommendations in the three TUBs were implemented. 8.3% of all recommendations showed a deviance. Most important reasons for the deviances were patient wish (36.5%), patient death (26%) and doctoral decision, due to the patient's comorbidities or side effects of the treatment (24.1%).Interestingly, deviance in all three tumor boards in total significantly decreased over time. CONCLUSIONS: Aim of the study was to clarify the use of tumor boards and find approaches to make them more efficient. Based on the results efficiency might be optimized by increased consideration of patients` preferences, improved presentation of patient-related data, more detailed documentation and further structuring of the tumor board meetings.

Implementation and Benefit Evaluation of Recommendations for Patient Safety in Ambulatory Surgical Care.

Objective: The aim of this study was to evaluate the degree of implementation of recommendations for patient safety in ambulatory surgical care and their benefit as perceived by surgeons in the ambulatory sector. Based on 2 practice recommendations issued by the Association of Statutory Health Insurance Physicians in Westphalia-Lippe, recommendations were formulated specifically for ambulatory surgery and distributed in 2013 to all physicians licensed to conduct ambulatory surgery in Westphalia-Lippe. Methods: We conducted a written survey covering all safety measures addressed by the 2 practice recommendations and assessed the degree of implementation and the perceived benefit for each of these measures as well as the strengths of the recommendations and the challenges of implementing them. The survey was distributed in late 2014 to 2 454 surgeons in the ambulatory setting. The survey period was 7 weeks. The analysis of the quantitative data was mainly descriptive and we conducted thematic summaries of free text answers to open-ended questions. Results: The participation rate was 17% (n=405). The recommendations were known to 86% of the respondents. The majority of recommended safety measures had been implemented systemically in more than 50% of the participating institutions. An increased interprofessional awareness of patient safety measurements was reported as the main impact of the recommendations. Respondents indicated further need for information and practice recommendations concerning the following topics: risk and error management, implementation of the Medical Devices Act, hygiene in medical practice and processing of instruments. Conclusion: This study highlights the valuable contribution practice recommendations can make to patient safety improvement in ambulatory surgical care. Their dissemination to other regions as well as to other ambulatory care settings such as family practice can therefore be recommended.

Adaptation in anaesthesia team coordination in response to a simulated critical event and its relationship to clinical performance.

BACKGROUND: Recent studies in anaesthesia and intensive care indicate that a team's ability to adapt its coordination activities to changing situational demands is crucial for effective teamwork and thus, safe patient care. This study addresses the relationship between adaptation of team coordination and markers of clinical performance in response to a critical event, particularly regarding which types of coordination activities are used and which team member engages in those coordination activities. METHODS: Video recordings of 15 two-person anaesthesia teams (anaesthesia trainee plus anaesthesia nurse) performing a simulated induction of general anaesthesia were coded, using a structured observation system for coordination activities. The simulation involved a critical event-asystole during laryngoscopy. Clinical performance was assessed using two separate reaction times related to the critical event. RESULTS: Analyses of variance revealed a significant effect of the critical event on team coordination: after the occurrence of the asystole, team members adapted their coordination activities by spending more time on information management-a specific type of coordination activity (F(1,28)=15.17, P=0.001). No significant effect was found for task management. The increase in information management was related to faster decisions regarding how to respond to the critical event, but only for trainees and not for nurses. CONCLUSIONS: Our findings support the claim that adaptation of coordination activities is related to improved team performance in healthcare. Moreover, adaptation and its relationship to team performance were found to vary with regard to type of coordination activities and team member.

Conceptualising barriers to incident reporting: a psychological framework.

BACKGROUND: Incident reporting systems are widely considered effective instruments for learning from incidents. However, research shows that many incidents are not reported by healthcare providers. OBJECTIVE: The lack of theoretical foundation in research on barriers to and motivators for incident reporting is addressed in this article, and a psychological framework of antecedents to staff's motivation (not) to report incidents is proposed. FRAMEWORK DEVELOPMENT: Concepts relevant for clinicians' motivation to report incidents were identified in psychological literature. Additionally, a literature review was conducted to extract barriers to incident reporting and cluster them into thematic groups. Barriers and motivators influencing clinicians' willingness to report were integrated and identified as an indicator for actual reporting behaviour. CONCLUSIONS: The proposed framework provides a basis for guiding future empirical studies that will improve our understanding of what encourages and what hinders clinicians to report incidents and, consequently, of areas for interventions to enhance reporting behaviour.

Teamwork and patient safety in dynamic domains of healthcare: a review of the literature.

AIMS/BACKGROUND: This review examines current research on teamwork in highly dynamic domains of healthcare such as operating rooms, intensive care, emergency medicine, or trauma and resuscitation teams with a focus on aspects relevant to the quality and safety of patient care. RESULTS: Evidence from three main areas of research supports the relationship between teamwork and patient safety: (1) Studies investigating the factors contributing to critical incidents and adverse events have shown that teamwork plays an important role in the causation and prevention of adverse events. (2) Research focusing on healthcare providers' perceptions of teamwork demonstrated that (a) staff's perceptions of teamwork and attitudes toward safety-relevant team behavior were related to the quality and safety of patient care and (b) perceptions of teamwork and leadership style are associated with staff well-being, which may impact clinician' ability to provide safe patient care. (3) Observational studies on teamwork behaviors related to high clinical performance have identified patterns of communication, coordination, and leadership that support effective teamwork. CONCLUSION: In recent years, research using diverse methodological approaches has led to significant progress in team research in healthcare. The challenge for future research is to further develop and validate instruments for team performance assessment and to develop sound theoretical models of team performance in dynamic medical domains integrating evidence from all three areas of team research identified in this review. This will help to improve team training efforts and aid the design of clinical work systems supporting effective teamwork and safe patient care.

Adaptive coordination in cardiac anaesthesia: a study of situational changes in coordination patterns using a new observation system.

Patient care in hospital settings requires coordinated team performance. Studies in other industries show that successful teams adapt their coordination processes to the situational task requirements. This prospective field study aimed to test a new observation system and investigate patterns of adaptive coordination within operating room teams. A trained observer recorded coordination activities during 24 cardiac surgery procedures. The study tested whether different patterns occur during different phases of and between different types of surgical procedures (two-way multivariate ANOVA with repeated measure). A statistically significant increase was found in clinical and coordination activities in phases of the operation with high task interdependence. The highest level of 'coordination via the work environment' (i.e. an implicit coordination mechanism) was recorded during the actual procedure on the beating heart. These findings prove the sensitivity of the observation system developed and evaluated in this study and provide insight into patterns of adaptive coordination in cardiac anaesthesia. This study furthers our understanding of adaptive coordination as a cornerstone of effective team performance in complex work environments. Using a new observation system, it describes patterns employed by health care professionals in response to changing task demands in an acute patient care setting.

[Patient safety and errors in medicine: development, prevention and analyses of incidents]. / Patientensicherheit und Fehler in der Medizin. Entstehung, Prävention und Analyse von Zwischenfällen.

"Patient safety" and "errors in medicine" are issues gaining more and more prominence in the eyes of the public. According to newer studies, errors in medicine are among the ten major causes of death in association with the whole area of health care. A new era has begun incorporating attention to a "systems" approach to deal with errors and their causes in the health system. In other high-risk domains with a high demand for safety (such as the nuclear power industry and aviation) many strategies to enhance safety have been established. It is time to study these strategies, to adapt them if necessary and apply them to the field of medicine. These strategies include: to teach people how errors evolve in complex working domains and how types of errors are classified; the introduction of critical incident reporting systems that are free of negative consequences for the reporters; the promotion of continuous medical education; and the development of generic problem-solving skills incorporating the extensive use of realistic simulators wherever possible. Interestingly, the field of anesthesiology--within which realistic simulators were developed--is referred to as a model for the new patient safety movement. Despite this proud track record in recent times though, there is still much to be done even in the field of anesthesiology. Overall though, the most important strategy towards a long-term improvement in patient safety will be a change of "culture" throughout the entire health care system. The "culture of blame" focused on individuals should be replaced by a "safety culture", that sees errors and critical incidents as a problem of the whole organization. The acceptance of human fallability and an open-minded non-punitive analysis of errors in the sense of a "preventive and proactive safety culture" should lead to solutions at the systemic level. This change in culture can only be achieved with a strong commitment from the highest levels of an organization. Patient safety must have the highest priority in the goals of the institution: "Primum nihil nocere"--"First, do not harm".

The T cell-dependent B cell immune response and germinal center reaction are intact in A-myb-deficient mice.

Expression of the protooncogene A-myb is restricted to the developing CNS, adult testes, breasts in late pregnancy, and germinal centers of secondary B cell follicles. The functional relevance of A-myb expression at three of these sites has been demonstrated previously via the generation and analysis of A-myb-deficient mice, which display behavioral abnormalities, male sterility, and perturbed breast development during pregnancy. In contrast, here we show that the germinal center response driven by T cell-dependent Ag immunization and the associated processes of Ab V gene somatic hypermutation, affinity maturation, and heavy chain class switching are overtly normal in A-myb-deficient mice. Nonetheless, these mice display mild splenic white pulp hypoplasia and blunted primary serum Ab responses, suggesting that although A-myb is not directly involved in the regulation of the memory B cell response, it may play a role in enhancing peripheral B cell survival or proliferative capacity.

Activation and anergy in bone marrow B cells of a novel immunoglobulin transgenic mouse that is both hapten specific and autoreactive.

Available evidence indicates that B cell tolerance is attained by receptor editing, anergy, or clonal deletion. Here, we describe a p-azophenylarsonate (Ars)-specific immunoglobulin transgenic mouse in which B cells become anergic as a consequence of cross-reaction with autoantigen in the bone marrow. Developing bone marrow B cells show no evidence of receptor editing but transiently upregulate activation markers and appear to undergo accelerated development. Mature B cells are present in normal numbers but are refractory to BCR-mediated induction of calcium mobilization, tyrosine phosphorylation, and antibody responses. Activation marker expression and acquisition of the anergic phenotype is prevented in bone marrow cultures by monovalent hapten. In this model, it appears that induction of anergy in B cells can be prevented by monovalent hapten competing with autoantigen for the binding site.

Enforced expression of Bcl-2 selectively perturbs negative selection of dual reactive antibodies.

We investigated the role of apoptosis in the development of B cell memory by analyzing the (p-azophenylarsonate) Ars response in a line of A strain mice in which expression of human Bcl-2 was enforced in the B cell compartment. Previous studies of the Ars immune response in these A. Bcl-2 mice, demonstrated that a large percentage of the antibodies expressed by the Ars induced memory B cell compartment had accumulated point mutations via somatic hypermutation that increased their affinity for both Ars and the autoantigen DNA ("dual reactive" antibodies). This was in sharp contrast to normal A strain mice which displayed no dual reactive B cells in their Ars induced memory B cell compartment. These data suggested that interference with apoptotic pathways regulated by Bcl-2 allows developing memory B cells that have acquired autoreactivity to bypass a peripheral tolerance checkpoint. Further studies of these mice, reported here, demonstrate that enforced expression of Bcl-2 does not alter serum antibody affinity maturation nor positive selection of B cells expressing somatically mutated antibody with an increased affinity for Ars. Moreover, the somatic hypermutation process was unaffected in A. Bcl-2 mice. Thus, enforced expression of Bcl-2 in A. Bcl-2 mice appears to selectively alter a negative selection process that operates during memory B cell differentiation.

Severe attenuation of the B cell immune response in Msh2-deficient mice.

Recently, results obtained from mice with targeted inactivations of postreplication DNA mismatch repair (MMR) genes have been interpreted to demonstrate a direct role for MMR in antibody variable (V) gene hypermutation. Here we show that mice that do not express the MMR factor Msh2 have wide-ranging defects in antigen-driven B cell responses. These include lack of progression of the germinal center (GC) reaction associated with increased intra-GC apoptosis, severely diminished antigen-specific immunoglobulin G responses, and near absence of anamnestic responses. Mice heterozygous for the Msh2 deficiency display an "intermediate" phenotype in these regards, suggesting that normal levels of Msh2 expression are critical for the B cell response. Interpretation of the impact of an MMR deficiency on the mechanism of V gene somatic hypermutation could be easily confounded by these perturbations.

T-cell receptor repertoires utilized in response to linear peptides representing an immunodominant MHC class II restricted T-cell epitope are far more diverse than that utilized in response to the same epitope in the nominal antigen.

Previous analyses of the T-cell receptor (TCR) repertoire utilized in response to the 1-102 fragment of the lambda cI repressor protein and specific for the immunodominant amino acid 12-26 region in the context of I-Ek, have shown this repertoire to be extremely restricted. In contrast, here we show that the TCR repertoires utilized in two strains of I-Ek expressing mice in response to two linear peptides representing this immunodominant region are diverse. Despite their extensive diversity, these repertoires are somewhat overlapping. In addition, structural similarities were observed between the full lambda cI fragment (1-102) and peptide elicited TCR repertoires, including frequent use of the Valpha2 family of gene segments, particularly among peptide (12-26) elicited TCRs cross-reactive with 1-102/I-Ek. Nevertheless, these data indicate that it may be difficult to mimic the immune response to an immunodominant epitope of a protein antigen via immunization with linear peptides containing the amino acid sequence of that epitope. Possible explanations for differences in the levels of TCR diversity among T cells responding to an epitope present in a nominal antigen as compared to T cells responding to linear peptide antigens containing this same epitope are discussed.

Bcl-2 obstructs negative selection of autoreactive, hypermutated antibody V regions during memory B cell development.

We analyzed the participation of a predominant B cell clonotype in the anti-arsonate immune response of mice in which Bcl-2 expression was enforced in B cells. Many of the antibodies expressed by the arsonate-induced memory compartment of these mice were "dual-reactive," displaying increased affinity acquired via V region somatic hypermutation for both arsonate and the autoantigen DNA. The hypermutated antibodies expressed by the anti-arsonate memory B cell compartment of normal mice have increased affinity for arsonate but lack measurable affinity for DNA. Thus, interference with apoptotic pathways allows developing memory B cells that have acquired autoreactivity to bypass a peripheral tolerance checkpoint. These data demonstrate that both positive and negative selection, working in concert with V gene somatic hypermutation, result in the "specificity maturation" of the antibody response.

A novel mechanism for B cell repertoire maturation based on response by B cell precursors to pre-B receptor assembly.

The expression of different sets of immunoglobulin specificities by fetal and adult B lymphocytes is a long-standing puzzle in immunology. Recently it has become clear that production of immunoglobulin mu heavy chain and subsequent assembly with a surrogate light chain to form the pre-B cell receptor complex is critical for development of B cells. Here we show that instead of promoting pre-B cell progression as in adult bone marrow, this complex inhibits pre-B cell growth in fetal liver. Curiously, we identify a fetal-associated VH11 mu heavy chain that allows continued pre-B proliferation in fetal liver. Interestingly, this heavy chain does not associate efficiently with a surrogate light chain, providing a previously unrecognized mechanism for skewing the expression of distinctive VH genes toward fetal through early neonatal life.

Graft-versus-myeloid leukemia responses following syngeneic and allogeneic bone marrow transplantation.

A model for investigating graft-versus-leukemia (GVL) activity following syngeneic and MHC-compatible allogeneic BMT has been developed in C57BL/6 (B6) mice with use of the c-myc retrovirus-transformed MMB3.19 myeloid leukemia line. The MMB3.19 line was derived from a B6 mouse and expresses monocyte/macrophage markers, including Mac-1, Mac-2, F4/80, and LFA-1, in addition to H-2 class I and class II molecules. A challenge dosage of 10(5) of these leukemia cells was found to be completely lethal when injected into irradiated (850 cGy) B6 recipients, 1 day after the transplantation of syngeneic donor T cell-depleted-bone marrow. The addition of T lymphocytes to the donor inoculum prolonged recipient survival, and both CD4+ and CD8+ subsets were found to be capable of mediating this GVL activity. For the MHC-compatible allogeneic model, the C3H.SW-->B6 (850 cGy) strain combination was utilized, in which CD8+ T cells are known to cause graft-versus-host disease directed to minor histocompatibility antigens expressed by the recipient. In this case, both CD(4+)- and CD(8+)-enriched T cells were found to be capable of mediating GVL activity to MMB3.19 challenge, particularly if donor mice were presensitized with leukemia cells. Of most significance, only the donor CD4+ T cells mediated a GVL effect without the apparent induction of graft-versus-host disease.

Monoclonal c-myc transformed macrophage cell lines. I. Heterogeneity in ability to process and present antigen.

Processing of proteins into immunogenic forms and their subsequent presentation to T cells are mediated by APC. Monocytes and macrophages have long been recognized as one of the APC types. However, little is known about whether functional heterogeneity in processing and presentation exist within the monocyte/macrophage population. Past difficulties in obtaining clonal representatives of these populations have limited investigations in this regard. The c-myc-containing retrovirus MRV, previously shown to immortalize murine macrophages, was used to generate a large panel of macrophage cell clones. Differences observed in cell surface antigen expression and morphology demonstrated phenotypic heterogeneity among these clones. Functional heterogeneity was also observed both before and after IFN-gamma and IL-4 stimulation. The clones differ in their capacity to present several nominal antigens to T cell hybridomas. When parallel variation in ability to present both a nominal antigen and a peptide representing the epitope for which a T cell hybridoma was specific was observed among the clones, this variation correlated with the levels of surface MHC class II antigen the clones expressed. In contrast, diversity in the ability to process and present certain nominal antigens among clones that all presented the corresponding antigenic peptide with similar efficiency did not appear to be due to differences in levels of surface MHC class II molecules. Our results suggest that the macrophage clones are heterogeneous in their ability to both process and present several antigens. The ability to obtain macrophage tissue culture cell lines displaying phenotypic and functional heterogeneity should allow insight into the impact of normal macrophage heterogeneity on the outcome of immune responses in vivo.

Hypermutation is observed only in antibody H chain V region transgenes that have recombined with endogenous immunoglobulin H DNA: implications for the location of cis-acting elements required for somatic mutation.

Mice with transgenes containing an antibody H chain V region (VHDJH) gene were used in an analysis of the cis-acting elements required for hypermutation of immunoglobulin (Ig) V genes. These transgenes can somatically recombine with endogenous IgH DNA, leading to the formation of functional heavy (H) chains partially encoded by the transgenic VHDJH. The transgenomes in the five different lines of mice analyzed contain as little as 150 bp, and as much as 2.8 kb of natural DNA flanking the 5' side of the VH and either 1.5 or 2.3 kb (including the intronic enhancer and 5' matrix attachment region [MAR]) flanking the 3' side of VH. Hybridomas were constructed from immunized transgenic mice, and transgenes present in these hybridomas that had or had not recombined to form functional H chain loci were sequenced. The data obtained show that: (a) the recombined transgenes contain hypermutated VH genes; and (b) among such transgenes, even those containing only 150 bp of natural VH 5' flanking sequence and several kilobases of 5' plasmid vector sequence display a frequency, distribution, and type of mutation characteristic of conventional IgH loci. The data also indicate that transgenic VHDJH genes that have not recombined with endogenous IgH DNA are not substrates for hypermutation, even if they are flanked by 2.8 kb of natural 5' DNA, and 2.3 kb of natural 3' DNA, including the JH2-JH4 region, a MAR, and the intronic enhancer. Collectively, the data suggest that sequences 5' of the VH promoter are dispensable, a VH promoter and the intronic IgH enhancer region are not sufficient, and a region(s) within or 3' of the IgH constant region locus is requisite, for hypermutation of Ig VH transgenes.

Regulation of the immune response to peptide antigens: differential induction of immediate-type hypersensitivity and T cell proliferation due to changes in either peptide structure or major histocompatibility complex haplotype.

The immunodominant CD4 T cell epitope of the bacteriophage lambda cI repressor protein in several inbred mouse strains can be represented by a peptide encompassing amino acids 12-26. Here, we show that this peptide, and a variety of its sequence variants, can induce immediate-type hypersensitivity in mice. 12-26 variants that differ by as little as single amino acid residues deviate greatly in their ability to induce hypersensitivity. Further, differences in major histocompatibility complex class II alleles appear to be as influential as changes in peptide structure in determining whether hypersensitivity is developed. The ability of a given peptide-class II combination to induce hypersensitivity correlates with production of peptide-specific antibody, but not with ability or inability to induce a T cell proliferative response. Administration of anti-interleukin 4 (IL-4) mAb prevents the development of hypersensitivity, and analysis of cytokine production by T cell hybridomas derived from peptide-immunized mice suggests that whether a given peptide-class II combination can induce hypersensitivity depends on its ability to induce IL-4 production. The data demonstrate that changes in the nature of the epitope(s) recognized by the CD4 T cell population can result in qualitative differences in the response elicited in this population, ultimately leading to dramatic quantitative and qualitative variations in the effector phase of the immune response.

Neuroleptic malignant syndrome associated with prochlorperazine.

Neuroleptic malignant syndrome occurred in a patient with AIDS being treated with prochlorperazine. We believe this to be the first report of this association. Recognition and specific treatment were delayed in part because of overlap in signs and symptoms of the underlying infectious process. The true incidence of prochlorperazine-induced NMS is unknown, and this reaction may be underrecognized in patients who often have other significant medical illnesses.