Improving difficult peripheral intravenous access requires thought, training and technology (DART3): a stepped-wedge, cluster randomised controlled trial protocol.

BACKGROUND: Peripheral intravenous catheters (PIVCs) are the most used invasive medical device in healthcare. Yet around half of insertion attempts are unsuccessful leading to delayed medical treatments and patient discomfort of harm. Ultrasound-guided PIVC (USGPIVC) insertion is an evidence-based intervention shown to improve insertion success especially in patients with Difficult IntraVenous Access (BMC Health Serv Res 22:220, 2022), however the implementation in some healthcare settings remains suboptimal. This study aims to co-design interventions that optimise ultrasound guided PIVC insertion in patients with DIVA, implement and evaluate these initiatives and develop scale up activities. METHODS: A stepped-wedge cluster randomized controlled trial will be conducted in three hospitals (two adult, one paediatric) in Queensland, Australia. The intervention will be rolled out across 12 distinct clusters (four per hospital). Intervention development will be guided by Michie's Behavior Change Wheel with the aim to increase local staff capability, opportunity, and motivation for appropriate, sustainable adoption of USGPIVC insertion. Eligible clusters include all wards or departments where > 10 PIVCs/week are typically inserted. All clusters will commence in the control (baseline) phase, then, one cluster per hospital will step up every two months, as feasible, to the implementation phase, where the intervention will be rolled out. Implementation strategies are tailored for each hospital by local investigators and advisory groups, through context assessments, staff surveys, and stakeholder interviews and informed by extensive consumer interviews and consultation. Outcome measures align with the RE-AIM framework including clinical-effectiveness outcomes (e.g., first-time PIVC insertion success for DIVA patients [primary outcome], number of insertion attempts); implementation outcomes (e.g., intervention fidelity, readiness assessment) and cost effectiveness outcomes. The Consolidated Framework for Implementation Research framework will be used to report the intervention as it was implemented; how people participated in and responded to the intervention; contextual influences and how the theory underpinning the intervention was realised and delivered at each site. A sustainability assessment will be undertaken at three- and six-months post intervention. DISCUSSION: Study findings will help define systematic solutions to implement DIVA identification and escalation tools aiming to address consumer dissatisfaction with current PIVC insertion practices. Such actionable knowledge is critical for implementation of scale-up activities. TRIAL REGISTRATION: Prospectively registered (Australian and New Zealand Clinical Trials Registry; ACTRN12621001497897).

Patient blood management in critically ill children undergoing cardiac surgery: A cohort study.

OBJECTIVE: The objective of this study was to audit current patient blood management practice in children throughout cardiac surgery and paediatric intensive care unit (PICU) admission. DESIGN: This was a prospective observational cohort study. SETTING: This was a single-centre study in the cardiac operating room (OR) and PICU in a major tertiary children's hospital in Australia. PATIENTS: Children undergoing corrective cardiac surgery and requiring admission to PICU for postoperative recovery were included in the study. MEASUREMENTS AND MAIN RESULTS: Fifty-six patients and 1779 blood sampling episodes were audited over a 7-month period. The median age was 9 months (interquartile range [IQR] = 1-102), with the majority (n = 30 [54%]) younger than 12 months. The median number of blood sampling episodes per patient per day was 6.6 (IQR = 5.8-8.0) in total, with a median of 5.0 (IQR = 4.0-7.5) episodes in the OR and 5.0 (IQR = 3.4-6.2) episodes per day throughout PICU admission. The most common reason for blood tests across both OR and PICU settings was arterial blood gas analysis (total median = 86%, IQR = 79-96). The overall median blood sampling volume per kg of bodyweight, patient, and day was 0.63 mL (IQR = 0.20-1.14) in total. Median blood loss for each patient was 3.5 mL/kg per patient per day (IQR = 1.7-5.6) with negligible amounts in the OR and a median of 3.6 mL/kg (IQR = 1.7-5.7) in the PICU. The median Cell Saver® transfusion volume was 9.9 mL/kg per patient per day (IQR = 4.0-19.1) in the OR. The overall median volume of other infusion products (albumin 4%, albumin 20%, packed red blood cells) received by each patient was 20.1 mL/kg (IQR = 10.7-36.4) per day. Sampling events and blood loss were positively associated with PICU stay. CONCLUSIONS: Patient blood management practices observed in this study largely conform to National Blood Authority guidelines. Further implementation projects and research are needed to accelerate implementation of known effective blood conservation strategies within paediatric critical care environments.

Quality measurement and surveillance platforms in critically ill children: A scoping review.

BACKGROUND/AIM: The objective of this study was to describe current surveillance platforms which support routine quality measurement in paediatric critical care. METHOD: Scoping review. The search strategy consisted of a traditional database and grey literature search as well as expert consultation. Surveillance platforms were eligible for inclusion if they collected measures of quality in critically ill children. RESULTS: The search strategy identified 21 surveillance platforms, collecting 57 unique outcome (70%), process (23%), and structural (7%) quality measures. Hospital-associated infections were the most commonly collected outcome measure across all platforms (n = 11; 52%). In general, case definitions were not harmonised across platforms, with the exception of nationally mandated hospital-associated infections (e.g., central line-associated blood stream infection). Data collection relied on manual coding. Platforms typically did not provide an evidence-based rationale for measures collected, with no identifiable reports of co-designed, consensus-derived measures or consumer involvement in measure selection or prioritisation. CONCLUSIONS: Quality measurement in critically ill children lacks uniformity in definition which limits local and international benchmarking. Current surveillance activities for critically ill children focus heavily on outcome measurement, with process, structural, and patient-reported measures largely overlooked. Long-term outcome measures were not routinely collected. Harmonisation of paediatric intensive care unit quality measures is needed and can be achieved using prioritisation and consensus/co-design methods.

The Impact of Phenotypic Heterogeneity on Chemotactic Self-Organisation.

The capacity to aggregate through chemosensitive movement forms a paradigm of self-organisation, with examples spanning cellular and animal systems. A basic mechanism assumes a phenotypically homogeneous population that secretes its own attractant, with the well known system introduced more than five decades ago by Keller and Segel proving resolutely popular in modelling studies. The typical assumption of population phenotypic homogeneity, however, often lies at odds with the heterogeneity of natural systems, where populations may comprise distinct phenotypes that vary according to their chemotactic ability, attractant secretion, etc. To initiate an understanding into how this diversity can impact on autoaggregation, we propose a simple extension to the classical Keller and Segel model, in which the population is divided into two distinct phenotypes: those performing chemotaxis and those producing attractant. Using a combination of linear stability analysis and numerical simulations, we demonstrate that switching between these phenotypic states alters the capacity of a population to self-aggregate. Further, we show that switching based on the local environment (population density or chemoattractant level) leads to diverse patterning and provides a route through which a population can effectively curb the size and density of an aggregate. We discuss the results in the context of real world examples of chemotactic aggregation, as well as theoretical aspects of the model such as global existence and blow-up of solutions.

Improving peripheral venous cannula insertion in children: a mixed methods study to develop the DIVA key.

OBJECTIVE: To develop and validate a difficult intravenous access risk assessment and escalation pathway, to increase first time intravenous insertion success in paediatrics. METHODS: Mixed methods underpinned by literature and co-production principles. Iterative development of the instrument was informed through semi-structured interviews and stakeholder workshops. The instrument includes a risk assessment, inserter skill self-assessment, and escalation pathways. Reproducibility, reliability, and acceptability were evaluated in a prospective cohort study at a quaternary paediatric hospital in Australia. RESULTS: Interview data (three parents, nine clinicians) uncovered two themes: i) Recognition of children with DIVA and subsequent escalation is ad hoc and problematic; and ii) Resources and training impact inserter confidence and ability. Three workshops were delivered at monthly intervals (February-April 2020) involving 21 stakeholders culminating in the co-production of the "DIVA Key". The DIVA Key was evaluated between May-December 2020 in 78 children; 156 clinicians. Seventy-eight paired assessments were undertaken with substantial agreement (concordance range = 81.5 to 83.0%) between the assessors. Interrater reliability of the DIVA risk assessment was moderate (kappa = 0.71, 95% CI 0.63-0.80). The DIVA Key predicted multiple insertion attempts for red (high risk) DIVA classification (relative risk ratio 5.7, 95% CI 1.2-27.1; reference low risk). Consumer and clinician satisfaction with DIVA Key was high (median (IQR) = 10 [8-10]; 8 [8-10 respectively). CONCLUSION: The DIVA Key is a straightforward, reliable instrument with inbuilt escalation pathway to support the identification of children with difficult intravenous access.

Comparison of midline catheters and peripherally inserted central catheters to reduce the need for general anesthesia in children with respiratory disease: A feasibility randomized controlled trial.

BACKGROUND: The optimal intravenous device for antibiotic administration for children with respiratory disease is uncertain. We assessed the feasibility of a randomized controlled trial comparing midline catheters with peripherally inserted central catheters. METHODS: Prospective, two-arm, feasibility randomized controlled trial in an Australian tertiary, pediatric hospital. Random assignment of 110 children (<18 years) to receive (i) midline catheter and (ii) peripherally inserted central catheters. Primary outcome was feasibility (eligibility, recruitment, retention, protocol adherence, and acceptability), and the primary clinical outcome was general anesthesia requirement for intravenous catheter insertion. SECONDARY OUTCOMES: insertion time, treatment delays, infusion efficiency, device failure, complications, and cost. RESULTS: There was 80% recruitment, 100% retention, no missing data, and high patient/staff acceptability. Mean patient experience assessed on a 0-10 numeric rating scale was 8.0 peripherally inserted central catheters and 9.0 (midline catheters), respectively. Participant eligibility was not achieved (49% of screened patients) and moderate protocol-adherence across groups (89% peripherally inserted central catheters vs. 76% midline catheter). Insertion of midline catheter for pulmonary optimization reduced the requirement for general anesthesia compared to peripherally inserted central catheters (10% vs. 69%; odds ratio = 0.01, 95% confidence interval: 0.00-0.09). Midline catheters failed more frequently (18.1 vs. 5.5 peripherally inserted central catheters per 1000 catheter-days); however, this reduced over trial duration. Midline catheter insertion compared to peripherally inserted central catheters saved AUD$1451 per pulmonary optimization episode. CONCLUSIONS: An efficacy trial is feasible with expanded eligibility criteria and intensive staff training when introducing a new device. Midline catheter for peripherally compatible infusions is acceptable to patients and staff, might negate the need for general anesthesia and results in significant cost savings.

Iterative community-driven development of a SARS-CoV-2 tissue simulator.

The 2019 novel coronavirus, SARS-CoV-2, is a pathogen of critical significance to international public health. Knowledge of the interplay between molecular-scale virus-receptor interactions, single-cell viral replication, intracellular-scale viral transport, and emergent tissue-scale viral propagation is limited. Moreover, little is known about immune system-virus-tissue interactions and how these can result in low-level (asymptomatic) infections in some cases and acute respiratory distress syndrome (ARDS) in others, particularly with respect to presentation in different age groups or pre-existing inflammatory risk factors. Given the nonlinear interactions within and among each of these processes, multiscale simulation models can shed light on the emergent dynamics that lead to divergent outcomes, identify actionable "choke points" for pharmacologic interventions, screen potential therapies, and identify potential biomarkers that differentiate patient outcomes. Given the complexity of the problem and the acute need for an actionable model to guide therapy discovery and optimization, we introduce and iteratively refine a prototype of a multiscale model of SARS-CoV-2 dynamics in lung tissue. The first prototype model was built and shared internationally as open source code and an online interactive model in under 12 hours, and community domain expertise is driving regular refinements. In a sustained community effort, this consortium is integrating data and expertise across virology, immunology, mathematical biology, quantitative systems physiology, cloud and high performance computing, and other domains to accelerate our response to this critical threat to international health. More broadly, this effort is creating a reusable, modular framework for studying viral replication and immune response in tissues, which can also potentially be adapted to related problems in immunology and immunotherapy.

A hybrid discrete-continuum approach to model Turing pattern formation.

Since its introduction in 1952, with a further refinement in 1972 by Gierer and Meinhardt, Turing's (pre-)pattern theory (the chemical basis of morphogenesis) has been widely applied to a number of areas in developmental biology, where evolving cell and tissue structures are naturally observed. The related pattern formation models normally comprise a system of reaction-diffusion equations for interacting chemical species (morphogens), whose heterogeneous distribution in some spatial domain acts as a template for cells to form some kind of pattern or structure through, for example, differentiation or proliferation induced by the chemical pre-pattern. Here we develop a hybrid discrete-continuum modelling framework for the formation of cellular patterns via the Turing mechanism. In this framework, a stochastic individual-based model of cell movement and proliferation is combined with a reaction-diffusion system for the concentrations of some morphogens. As an illustrative example, we focus on a model in which the dynamics of the morphogens are governed by an activator-inhibitor system that gives rise to Turing pre-patterns. The cells then interact with the morphogens in their local area through either of two forms of chemically-dependent cell action: Chemotaxis and chemically-controlled proliferation. We begin by considering such a hybrid model posed on static spatial domains, and then turn to the case of growing domains. In both cases, we formally derive the corresponding deterministic continuum limit and show that that there is an excellent quantitative match between the spatial patterns produced by the stochastic individual-based model and its deterministic continuum counterpart, when sufficiently large numbers of cells are considered. This paper is intended to present a proof of concept for the ideas underlying the modelling framework, with the aim to then apply the related methods to the study of specific patterning and morphogenetic processes in the future.

From a discrete model of chemotaxis with volume-filling to a generalized Patlak-Keller-Segel model.

We present a discrete model of chemotaxis whereby cells responding to a chemoattractant are seen as individual agents whose movement is described through a set of rules that result in a biased random walk. In order to take into account possible alterations in cellular motility observed at high cell densities (i.e. volume-filling), we let the probabilities of cell movement be modulated by a decaying function of the cell density. We formally show that a general form of the celebrated Patlak-Keller-Segel (PKS) model of chemotaxis can be formally derived as the appropriate continuum limit of this discrete model. The family of steady-state solutions of such a generalized PKS model are characterized and the conditions for the emergence of spatial patterns are studied via linear stability analysis. Moreover, we carry out a systematic quantitative comparison between numerical simulations of the discrete model and numerical solutions of the corresponding PKS model, both in one and in two spatial dimensions. The results obtained indicate that there is excellent quantitative agreement between the spatial patterns produced by the two models. Finally, we numerically show that the outcomes of the two models faithfully replicate those of the classical PKS model in a suitable asymptotic regime.

Bridging the gap between individual-based and continuum models of growing cell populations.

Continuum models for the spatial dynamics of growing cell populations have been widely used to investigate the mechanisms underpinning tissue development and tumour invasion. These models consist of nonlinear partial differential equations that describe the evolution of cellular densities in response to pressure gradients generated by population growth. Little prior work has explored the relation between such continuum models and related single-cell-based models. We present here a simple stochastic individual-based model for the spatial dynamics of multicellular systems whereby cells undergo pressure-driven movement and pressure-dependent proliferation. We show that nonlinear partial differential equations commonly used to model the spatial dynamics of growing cell populations can be formally derived from the branching random walk that underlies our discrete model. Moreover, we carry out a systematic comparison between the individual-based model and its continuum counterparts, both in the case of one single cell population and in the case of multiple cell populations with different biophysical properties. The outcomes of our comparative study demonstrate that the results of computational simulations of the individual-based model faithfully mirror the qualitative and quantitative properties of the solutions to the corresponding nonlinear partial differential equations. Ultimately, these results illustrate how the simple rules governing the dynamics of single cells in our individual-based model can lead to the emergence of complex spatial patterns of population growth observed in continuum models.

Insertion, management, and complications associated with arterial catheters in paediatric intensive care: A clinical audit.

INTRODUCTION: Peripheral arterial catheters (PAC) are used for haemodynamic monitoring and blood sampling in paediatric critical care. Limited data are available regarding PAC insertion and management practices, and how they relate to device function and failure. This information is necessary to inform future interventional research. OBJECTIVES: The primary objective of this study was to describe PAC insertion and management practices, and associated complications. Secondary objectives were to determine patient and clinical characteristics associated with risk of PAC successful insertion and failure. METHODS: A prospective, observational study was conducted in the anaesthetic department and paediatric intensive care unit of a tertiary paediatric facility. Data were collected on PAC insertion, PAC management and PAC removal. Standard incidence and prevalence were calculated per 1,000 device days. Risk factors for multiple insertions and PAC failure were identified using Cox regression. RESULTS: A total of 100 catheters in 89 children were examined capturing 472 device days. PACs were primarily inserted for blood sampling (78%) in the radial artery (78%) using ultrasound guidance (67%), with 31% inserted on first attempt. Heparin saline solution was used in 82% of devices. Median catheter dwell was 50.6 hours (IQR 24.0 - 158.0), with PAC failure occurring in 19 devices (20%), at a rate of 40.2 per 1000 catheter days (95% CI 25.7 - 63.1). Arm board immobilisation (HR 2.9; 95% CI 1.02-8.02; p = 0.05), higher PIM3 score (HR 1.06; 95% CI 1.03-1.09; p < 0.01) was associated with an increased the risk of PAC failure, and non-2% chlorhexidine antisepsis was associated with a decrease in PAC failure (HR 0.32; 95% CI 0.11-0.96; p = 0.04), in univariate analysis. CONCLUSIONS: PAC insertion is challenging, and failure is common. Prospective clinical trial data is needed to identify high risk patient groups and to develop interventions which optimise practices, thereby reducing failure.

Difficult Peripheral Venous Access in Children: An International Survey and Critical Appraisal of Assessment Tools and Escalation Pathways.

BACKGROUND: Peripheral venous cannulation is considered a routine procedure, yet 50% of first attempt insertions fail, necessitating repeat insertion attempts. Identification of children with difficult intravenous access (DIVA) can help promote prompt escalation to an appropriately skilled clinician. OBJECTIVE: To describe current international practice regarding the identification and management of children with DIVA, and to systematically review clinical tools and clinical pathways for children with DIVA. METHODS: A cross-sectional, international survey; followed by a systematic review and critical appraisal of clinical pathways using the Appraisal of Guidelines for Research Evaluation (AGREE) II checklist. RESULTS: A total of 148 clinicians from eight countries completed the survey. The majority were nurses (n = 92; 62%), practicing as vascular access specialists (n = 27; 18%). Twenty-three respondents (16%) reported using a DIVA tool, of which the DIVA Score was most common (n = 5; 22%). Five clinical pathways were identified from the survey and review. Based on the AGREE II domains, pathways generally scored well for scope and purpose, and for clarity of presentation areas. Information on the rigor of development and editorial independence was infrequently detailed. Based on AGREE II findings, one pathway was recommended for clinical practice, and four were recommended for use with modification. CONCLUSIONS: Resources for the identification and escalation of children with DIVA are not standardized or consistently used. Further work is needed to streamline processes for DIVA identification and escalation to the appropriate clinician, with technology-assisted insertion capability. This will enhance patient experiences and reduce harm from multiple insertion attempts. CLINICAL RELEVANCE: Multiple failed insertion attempts come at great cost to the child, family, and healthcare service. Early identification and management of the child with DIVA can ensure prompt escalation and management, improving the patient and family experience.

Innovation in Central Venous Access Device Security: A Pilot Randomized Controlled Trial in Pediatric Critical Care.

OBJECTIVES: Central venous access devices enable many treatments during critical illness; however, 25% of pediatric central venous access devices fail before completion of treatment due to infection, thrombosis, dislodgement, and occlusion. This is frequently attributed to inadequate securement and dressing of the device; however, high-quality research evaluating pediatric central venous access device securement innovation to prevent central venous access device failure is scarce. This study aimed to establish the feasibility of a definitive randomized control trial examining the effectiveness of current and new technologies to secure central venous access devices in pediatrics. DESIGN: Single-center, parallel group, superiority, pilot randomized control trial. SETTING: Anesthetic and intensive care departments of a tertiary pediatric hospital SUBJECTS:: One-hundred eighty pediatric patients with nontunneled central venous access device INTERVENTIONS:: Participants were randomized to receive central venous access device securement via standard care (bordered polyurethane dressing, with prolene sutures, chlorhexidine gluconate disc), tissue adhesive (Histoacryl, B Braun, Melsungen, Germany) in addition to standard care; or integrated dressing securement (SorbaView SHIELD [Centurion Medical Products, Franklin, MA], with prolene sutures and chlorhexidine gluconate disc). OUTCOMES: Primary: Feasibility (including effect size estimates, acceptability); central venous access device failure; central venous access device complications; secondary: individual central venous access device complications, skin damage, dressing performance, and product cost. MEASUREMENTS AND MAIN RESULTS: Feasibility criteria were achieved as recruitment occurred with acceptable eligibility, recruitment, missing data, and attrition rates, as well as good protocol adherence. Family members and staff-reported comparable levels of acceptability between study arms; however, tissue adhesive was reported as the most difficult to apply. Overall, 6% of central venous access devices failed, including 6% (3/54; incident rate, 13.2 per 1,000 catheter days) standard care, 2% (1/56; incident rate, 3.65 per 1,000 catheter days) integrated, and 8% (5/59; 25.0 per 1,000 catheter days) tissue adhesive. CONCLUSIONS: It is feasible to conduct an efficacy randomized control trial of the studied interventions. Further research is required to definitively identify clinical, cost-effective methods to prevent central venous access device failure by examining new dressing and securement technologies and techniques.

Building a Global, Pediatric Vascular Access Registry: A Scoping Review of Trial Outcomes and Quality Indicators to Inform Evidence-Based Practice.

BACKGROUND: Internationally, there is a lack of comparative vascular access (VA) data for pediatric clinicians and organizations to benchmark outcomes, evaluate quality initiatives, and improve practice. A VA registry is needed to address these knowledge and data capture gaps. OBJECTIVES: To determine the range and heterogeneity of VA outcome measures or quality indicators reported in randomized controlled trials (RCTs) and clinical registries, to inform development of a homogeneous, reliable, minimum dataset for a pediatric VA registry. METHODS: Scoping review framework. A systematic search for RCTs reporting VA outcomes in pediatrics and neonates was undertaken in the Cochrane library, EMBASE, CINAHL, PubMed, MEDLINE, and EBSCO using a medical subject headings and key words related to VA and pediatrics. We included RCTs of children (0-18 years) reporting any VA outcome. We identified clinical registries reporting VA data in children (0-18) through web-based searches using key words related to VA and clinical or quality registries. Additional registries were identified through peer consultation. The frequency and scope of outcome measures and quality indicators were extracted from trials and registries and evaluated. RESULTS: From 93 RCTs included, 214 different VA measures were reported, reflecting 14 outcome domains. The most commonly reported outcome domains were insertion (44 RCTs; 47%), noninfectious complications (33 RCTs; 35%), and infectious complications (30 RCTs; 32%). Of the 22 registries identified, VA-associated infection was the main quality indicator routinely collected (12 registries; 55%). Outcomes such as mechanical complications and patient-reported outcomes were infrequently collected. LINKING EVIDENCE TO ACTION: Vascular access outcomes reported in pediatric and neonatal RCTs are highly heterogeneous. Internationally, clinical registries currently collect minimal VA data with the exception of infection outcomes. A core dataset of reliable, relevant measures to children and clinicians for VA device quality is needed. This will enable a VA registry that facilitates inter-institutional and international benchmarking.

Quantitative Predictive Modelling Approaches to Understanding Rheumatoid Arthritis: A Brief Review.

Rheumatoid arthritis is a chronic autoimmune disease that is a major public health challenge. The disease is characterised by inflammation of synovial joints and cartilage erosion, which lead to chronic pain, poor life quality and, in some cases, mortality. Understanding the biological mechanisms behind the progression of the disease, as well as developing new methods for quantitative predictions of disease progression in the presence/absence of various therapies is important for the success of therapeutic approaches. The aim of this study is to review various quantitative predictive modelling approaches for understanding rheumatoid arthritis. To this end, we start by briefly discussing the biology of this disease and some current treatment approaches, as well as emphasising some of the open problems in the field. Then, we review various mathematical mechanistic models derived to address some of these open problems. We discuss models that investigate the biological mechanisms behind the progression of the disease, as well as pharmacokinetic and pharmacodynamic models for various drug therapies. Furthermore, we highlight models aimed at optimising the costs of the treatments while taking into consideration the evolution of the disease and potential complications.

Modelling the Immune Response to Cancer: An Individual-Based Approach Accounting for the Difference in Movement Between Inactive and Activated T Cells.

A growing body of experimental evidence indicates that immune cells move in an unrestricted search pattern if they are in the pre-activated state, whilst they tend to stay within a more restricted area upon activation induced by the presence of tumour antigens. This change in movement is not often considered in the existing mathematical models of the interactions between immune cells and cancer cells. With the aim to fill such a gap in the existing literature, in this work we present a spatially structured individual-based model of tumour-immune competition that takes explicitly into account the difference in movement between inactive and activated immune cells. In our model, a Lévy walk is used to capture the movement of inactive immune cells, whereas Brownian motion is used to describe the movement of antigen-activated immune cells. The effects of activation of immune cells, the proliferation of cancer cells and the immune destruction of cancer cells are also modelled. We illustrate the ability of our model to reproduce qualitatively the spatial trajectories of immune cells observed in experimental data of single-cell tracking. Computational simulations of our model further clarify the conditions for the onset of a successful immune action against cancer cells and may suggest possible targets to improve the efficacy of cancer immunotherapy. Overall, our theoretical work highlights the importance of taking into account spatial interactions when modelling the immune response to cancer cells.

Pelvic examination leads to changed clinical management in very few women diagnosed with asymptomatic chlamydia infection.

The present study aimed to determine whether pelvic examinations change clinical management of women with asymptomatic chlamydia infection. Records for women with asymptomatic chlamydia who underwent a pelvic examination at a sexual health clinic in Melbourne, Australia (January 2006 to June 2007) were analysed retrospectively. Of 91 cases, 31 (34%) warranted examination; one woman (1%; 95% confidence interval: 0.5%, 6.4%) had muco-purulent cervicitis and mild tenderness, and was treated for possible pelvic inflammatory disease. These data suggest that a pelvic examination will lead to changes in treatment for very few women diagnosed with asymptomatic chlamydia infection.