Weighting Low-Intensity MS/MS Ions and m/z Frequency for Spectral Library Annotation.

Calculating spectral similarity is a fundamental step in MS/MS data analysis in untargeted metabolomics experiments, as it facilitates the identification of related spectra and the annotation of compounds. To improve matching accuracy when querying an experimental mass spectrum against a spectral library, previous approaches have proposed increasing peak intensities for high m/z ranges. These high m/z values tend to be smaller in magnitude, yet they offer more crucial information for identifying the chemical structure. Here, we evaluate the impact of using these weights for identifying structurally related compounds and mass spectral library searches. Additionally, we propose a weighting approach that (i) takes into account the frequency of the m/z values within a spectral library in order to assign higher importance to the most common peaks and (ii) increases the intensity of lower peaks, similar to previous approaches. To demonstrate our approach, we applied weighting preprocessing to modified cosine, entropy, and fidelity distance metrics and benchmarked it against previously reported weights. Our results demonstrate how weighting-based preprocessing can assist in annotating the structure of unknown spectra as well as identifying structurally similar compounds. Finally, we examined scenarios in which the utilization of weights resulted in diminished performance, pinpointing spectral features where the application of weights might be detrimental.

Exploring the known chemical space of the plant kingdom: insights into taxonomic patterns, knowledge gaps, and bioactive regions.

Plants are one of the primary sources of natural products for drug development. However, despite centuries of research, only a limited region of the phytochemical space has been studied. To understand the scope of what is explored versus unexplored in the phytochemical space, we begin by reconstructing the known chemical space of the plant kingdom, mapping the distribution of secondary metabolites, chemical classes, and plants traditionally used for medicinal purposes (i.e., medicinal plants) across various levels of the taxonomy. We identify hotspot taxonomic clades occupied by a large proportion of medicinal plants and characterized secondary metabolites, as well as clades requiring further characterization with regard to their chemical composition. In a complementary analysis, we build a chemotaxonomy which has a high level of concordance with the taxonomy at the genus level, highlighting the close relationship between chemical profiles and evolutionary relationships within the plant kingdom. Next, we delve into regions of the phytochemical space with known bioactivity that have been used in modern drug discovery. While we find that the vast majority of approved drugs from phytochemicals are derived from known medicinal plants, we also show that medicinal and non-medicinal plants do not occupy distinct regions of the known phytochemical landscape and their phytochemicals exhibit properties similar to bioactive compounds. Moreover, we also reveal that only a few thousand phytochemicals have been screened for bioactivity and that there are hundreds of known bioactive compounds present in both medicinal and non-medicinal plants, suggesting that non-medicinal plants also have potential therapeutic applications. Overall, these results support the hypothesis that there are many plants with medicinal properties awaiting discovery.

Modern drug discovery using ethnobotany: A large-scale cross-cultural analysis of traditional medicine reveals common therapeutic uses.

For millennia, numerous cultures and civilizations have relied on traditional remedies derived from plants to treat a wide range of conditions and ailments. Here, we systematically analyzed ethnobotanical patterns across taxonomically related plants, demonstrating that congeneric medicinal plants are more likely to be used for treating similar indications. Next, we reconstructed the phytochemical space covered by medicinal plants to reveal that (i) taxonomically related medicinal plants cover a similar phytochemical space, and (ii) chemical similarity correlates with similar therapeutic usage. Lastly, we present several case scenarios illustrating how mining this information can be used for drug discovery applications, including: (i) investigating taxonomic hotspots around particular indications, (ii) exploring shared patterns of congeneric plants located in different geographic areas, but which have been used to treat the same indications, and (iii) showing the concordance between ethnobotanical patterns among non-taxonomically related plants and the presence of shared bioactive phytochemicals.

Human nuclear hormone receptor activity contributes to malaria parasite liver stage development.

Chemical genetic approaches have had a transformative impact on discovery of drug targets for malaria but have primarily been used for parasite targets. To identify human pathways required for intrahepatic development of parasite, we implemented multiplex cytological profiling of malaria infected hepatocytes treated with liver stage active compounds. Some compounds, including MMV1088447 and MMV1346624, exhibited profiles similar to cells treated with nuclear hormone receptor (NHR) agonist/antagonists. siRNAs targeting human NHRs, or their signaling partners identified eight genes that were critical for Plasmodium berghei infection. Knockdown of NR1D2, a host NHR, significantly impaired parasite growth by downregulation of host lipid metabolism. Importantly, treatment with MMV1088447 and MMV1346624 but not other antimalarials, phenocopied the lipid metabolism defect of NR1D2 knockdown. Our data underlines the use of high-content imaging for host-cellular pathway deconvolution, highlights host lipid metabolism as a drug-able human pathway and provides new chemical biology tools for studying host-parasite interactions.

On the correspondence between the transcriptomic response of a compound and its effects on its targets.

Better understanding the transcriptomic response produced by a compound perturbing its targets can shed light on the underlying biological processes regulated by the compound. However, establishing the relationship between the induced transcriptomic response and the target of a compound is non-trivial, partly because targets are rarely differentially expressed. Therefore, connecting both modalities requires orthogonal information (e.g., pathway or functional information). Here, we present a comprehensive study aimed at exploring this relationship by leveraging thousands of transcriptomic experiments and target data for over 2000 compounds. Firstly, we confirm that compound-target information does not correlate as expected with the transcriptomic signatures induced by a compound. However, we reveal how the concordance between both modalities increases by connecting pathway and target information. Additionally, we investigate whether compounds that target the same proteins induce a similar transcriptomic response and conversely, whether compounds with similar transcriptomic responses share the same target proteins. While our findings suggest that this is generally not the case, we did observe that compounds with similar transcriptomic profiles are more likely to share at least one protein target and common therapeutic applications. Finally, we demonstrate how to exploit the relationship between both modalities for mechanism of action deconvolution by presenting a case scenario involving a few compound pairs with high similarity.

Ensembles of knowledge graph embedding models improve predictions for drug discovery.

Recent advances in Knowledge Graphs (KGs) and Knowledge Graph Embedding Models (KGEMs) have led to their adoption in a broad range of fields and applications. The current publishing system in machine learning requires newly introduced KGEMs to achieve state-of-the-art performance, surpassing at least one benchmark in order to be published. Despite this, dozens of novel architectures are published every year, making it challenging for users, even within the field, to deduce the most suitable configuration for a given application. A typical biomedical application of KGEMs is drug-disease prediction in the context of drug discovery, in which a KGEM is trained to predict triples linking drugs and diseases. These predictions can be later tested in clinical trials following extensive experimental validation. However, given the infeasibility of evaluating each of these predictions and that only a minimal number of candidates can be experimentally tested, models that yield higher precision on the top prioritized triples are preferred. In this paper, we apply the concept of ensemble learning on KGEMs for drug discovery to assess whether combining the predictions of several models can lead to an overall improvement in predictive performance. First, we trained and benchmarked 10 KGEMs to predict drug-disease triples on two independent biomedical KGs designed for drug discovery. Following, we applied different ensemble methods that aggregate the predictions of these models by leveraging the distribution or the position of the predicted triple scores. We then demonstrate how the ensemble models can achieve better results than the original KGEMs by benchmarking the precision (i.e., number of true positives prioritized) of their top predictions. Lastly, we released the source code presented in this work at https://github.com/enveda/kgem-ensembles-in-drug-discovery.

Causal reasoning over knowledge graphs leveraging drug-perturbed and disease-specific transcriptomic signatures for drug discovery.

Network-based approaches are becoming increasingly popular for drug discovery as they provide a systems-level overview of the mechanisms underlying disease pathophysiology. They have demonstrated significant early promise over other methods of biological data representation, such as in target discovery, side effect prediction and drug repurposing. In parallel, an explosion of -omics data for the deep characterization of biological systems routinely uncovers molecular signatures of disease for similar applications. Here, we present RPath, a novel algorithm that prioritizes drugs for a given disease by reasoning over causal paths in a knowledge graph (KG), guided by both drug-perturbed as well as disease-specific transcriptomic signatures. First, our approach identifies the causal paths that connect a drug to a particular disease. Next, it reasons over these paths to identify those that correlate with the transcriptional signatures observed in a drug-perturbation experiment, and anti-correlate to signatures observed in the disease of interest. The paths which match this signature profile are then proposed to represent the mechanism of action of the drug. We demonstrate how RPath consistently prioritizes clinically investigated drug-disease pairs on multiple datasets and KGs, achieving better performance over other similar methodologies. Furthermore, we present two case studies showing how one can deconvolute the predictions made by RPath as well as predict novel targets.

Slipping rib syndrome.

Slipping rib syndrome (SRS) is an underdiagnosed condition that can lead to debilitating lower chest and upper abdominal pain (Am J Med Sci 2019; 357: 168). It is caused by hypermobility of the anterior ends of the costal cartilages of false ribs, allowing the eighth to tenth ribs to slip under the rib above, giving its name (Semin Pediatr Surg 2018; 27: 183). Failure to recognize this syndrome can expose patients to extensive and unnecessary investigations for unclear symptoms. Although more commonly reported in adults, SRS is a relatively uncommon but recognized cause of lower chest or upper abdomen pain in adolescence (Pediatr Anesth 2001; 11: 740). It is important for clinicians to familiarize themselves with and consider the diagnosis of SRS when assessing and managing adolescents with persistent thoracic pain. We present a case of a 14-year-old girl with unresolved thoracic pain for more than 4 years and was ultimately diagnosed with SRS.

Corrigendum to: Multimorbidity through the lens of life-limiting illness: how helpful are Australian clinical practice guidelines to its management in primary care?

This study assessed Australian clinical practice guidelines for life-limiting index conditions for the extent to which they acknowledged comorbidities and framed management recommendations within the context of older age and reduced life expectancy. A comprehensive search identified current, evidence-based Australian guidelines for chronic life-limiting conditions directed at general practitioners. Guideline content was analysed qualitatively before comorbidity acknowledgements were quantified using a 17-item checklist. Full guidelines were quality appraised using AGREE-II. Ten documents covering chronic obstructive pulmonary disease, heart failure, cancer pain, dementia and palliative care in aged care were identified. Most guidelines addressed one 'comorbid' condition and prompted clinicians to consider patient quality of life and personal preferences. Fewer addressed burden of treatment and half suggested modifying treatments to account for limited life expectancy, age or time horizon to benefit. Half warned of potential adverse drug interactions. Guidelines were of moderate to very high quality. Guidelines naturally prioritised their index condition, directing attention to only the most common comorbidities. However, there may be scope to include more condition-agnostic guidance on multimorbidity management. This might be modelled on the 'guiding principles' approach now emerging internationally from organisations such as the American Geriatrics Society in response to increasing multimorbidity prevalence and evidence limitations.

The adequacy of fluoroscopic upper gastrointestinal studies for suspected intestinal volvulus in a tertiary care centre vs. secondary centres: A regional multicentre study.

INTRODUCTION: Early diagnosis and treatment of intestinal volvulus are important to reduce morbidity. A fluoroscopic upper GI study is the gold standard for diagnosis and may be performed in a secondary or tertiary care centre prior to surgery. It is important the reporting radiologist is confident in the findings. We aim to assess whether there is any difference in confidence and study quality between paediatric and general radiologists who work in secondary or tertiary care centres. METHODS: Retrospective review of initial radiology reports and blinded review of the study images by paediatric radiologists. RESULTS: A total of 277 children underwent a fluoroscopic study for intestinal volvulus over a four-year period. The majority were performed at a tertiary care centre, by paediatric radiologists. The confidence of initial reporting was higher in paediatric than general radiologists despite whether they worked in a secondary or tertiary care centre (P-value < 0.001). On retrospective review, studies performed by paediatric radiologists were rated as having a higher confidence in identifying the location of the duodenojejunal flexure. General radiologists tended to have a slightly higher rate of repeat studies but still low at 2.2%. Despite this, there was no significant difference in the diagnosis rates and secondary centre general radiologists excluded malrotation in 62% of studies likely reducing transfer rates. CONCLUSION: Confidence in initial reporting and on review of the duodenojejunal flexure location in suspected intestinal volvulus is higher in paediatric radiologists compared with general radiologists, although diagnosis rates are no different.

A comparison of 2- and 3-dimensional mandibular superimposition techniques against Björk's structural superimposition method.

INTRODUCTION: The purpose of this research was to compare mandibular growth rotation relative to the cranial base in different vertical facial patterns on the basis of multiple 2-dimensional (2D) and 3-dimensional (3D) superimposition methods. METHODS: Cone-beam computed tomography (CBCT) images taken at a mean interval of 54.8 ± 16.8 months were assessed from a sample of 70 growing patients. Three mandibular superimposition methods were compared against Björk's structural method: (1) a 2D landmark method (2D-M1), (2) a voxel-based 3D method based on a previously reported method (3D-M1), and (3) a voxel-based 3D method incorporating symphyseal structures as references (3D-M2). After superimposition, the relative change in cranial base lines as depicted in sagittal views were measured for true mandibular rotation. Agreement between methods was assessed with Lin's concordance correlation coefficient, Bland-Altman's limits of agreement, and the Bradley-Blackwood test. RESULTS: Lin's concordance correlation coefficients ranged between 0.924 for the 2D-M1 method, 0.695 for the 3D-M1 method, and 0.965 for the 3D-M2 method. Bland-Altman limits of agreement were wide for all but the 3D-M2 method. Finally, the Bradley-Blackwood test of equality of means and variances was significant in all except the 3D-M2 method. CONCLUSIONS: For time intervals between CBCT volume acquisitions >3 years, the use of the 2D-M1 and 3D-M1 methods is not recommended. There was a high concordance between the 3D-M2 method and Björk's structural method when assessing mandibular growth rotation using relative changes in cranial base lines. The high concordance was displayed across all vertical facial types and for all time differences between first and second CBCT data acquisitions.

Multimorbidity through the lens of life-limiting illness: how helpful are Australian clinical practice guidelines to its management in primary care?

This study assessed Australian clinical practice guidelines for life-limiting index conditions for the extent to which they acknowledged comorbidities and framed management recommendations within the context of older age and reduced life expectancy. A comprehensive search identified current, evidence-based Australian guidelines for chronic life-limiting conditions directed at general practitioners. Guideline content was analysed qualitatively before comorbidity acknowledgements were quantified using a 17-item checklist. Full guidelines were quality appraised using AGREE-II. Ten documents covering chronic obstructive pulmonary disease, heart failure, cancer pain, dementia and palliative care in aged care were identified. Most guidelines addressed one 'comorbid' condition and prompted clinicians to consider patient quality of life and personal preferences. Fewer addressed burden of treatment and half suggested modifying treatments to account for limited life expectancy, age or time horizon to benefit. Half warned of potential adverse drug interactions. Guidelines were of moderate to very high quality. Guidelines naturally prioritised their index condition, directing attention to only the most common comorbidities. However, there may be scope to include more condition-agnostic guidance on multimorbidity management. This might be modelled on the 'guiding principles' approach now emerging internationally from organisations such as the American Geriatrics Society in response to increasing multimorbidity prevalence and evidence limitations.

Bolstering General Practitioner Palliative Care: A Critical Review of Support Provided by Australian Guidelines for Life-Limiting Chronic Conditions.

General practitioners (GPs) are increasingly expected to provide palliative care as ageing populations put pressure on specialist services. Some GPs, however, cite barriers to providing this care including prognostication challenges and lack of confidence. Palliative care content within clinical practice guidelines might serve as an opportunistic source of informational support to GPs. This review analysed palliative care content within Australian guidelines for life-limiting conditions to determine the extent to which it might satisfy GPs' stated information needs and support them to provide quality end-of-life care. Six databases and guideline repositories were searched (2011-2018). Eligible guidelines were those for a GP audience and explicitly based on an appraisal of all available evidence. Content was mapped against an established palliative care domain framework (PEPSI-COLA) and quality was assessed using AGREE-II. The nine guidelines meeting inclusion criteria were heterogenous in scope and depth of palliative care domain coverage. The 'communication' needs domain was best addressed while patient physical and emotional needs were variably covered. Spiritual, out-of-hours, terminal care and aftercare content was scant. Few guidelines addressed areas GPs are known to find challenging or acknowledged useful decision-support tools. A template covering important domains might reduce content variability across guidelines.

Dental arch relationship outcomes for children with complete unilateral and complete bilateral cleft lip and palate in New Zealand.

OBJECTIVES: To evaluate dental arch relationships of patients with complete unilateral and complete bilateral cleft lip and palate (CUCLP/CBCLP) in New Zealand. SETTING AND SAMPLE POPULATION: Retrospective nationwide observational outcomes study involving 100 CUCLP and 32 CBCLP non-syndromic patients. MATERIAL AND METHODS: Four calibrated assessors, blinded to the origin of the randomized digital models, used the GOSLON (UCLP) and the Bauru-BCLP (BCLP) Yardsticks and a 100 mm visual analogue scale (VAS) (UCLP&BCLP) to assess dental arch relationships. Weighted Kappa statistics were used to determine the intra- and inter-rater reliability for the GOSLON/Bauru-BCLP Yardsticks and correlations for the VAS. RESULTS: Intra-rater reliability ranged from 0.57 to 0.88 (GOSLON), 0.62-0.84 (Bauru-BCLP) and 0.45-0.93 (VAS). Inter-rater reliability ranged from 0.62 to 0.86, (GOSLON), 0.48-0.75 (Bauru-BCLP) and 0.64-0.93 (VAS). Of the 100 CUCLP models, 46% had poor/very poor, 28% fair and 26% had good/very good dental arch relationships. Of the 32 CBCLP models, 37.5% were poor/very poor, 40.6% fair and 21.9% had good/very good dental arch relationships. The mean CUCLP VAS score was 50.5 mm (SD 19.9 mm) whilst the mean CBCLP VAS score was 40.0 mm (SD 22.0 mm) and both showed a strong relationship with their respective Yardstick scorings. CONCLUSION: The dental arch relationships of children in New Zealand with CUCLP are similar to those centres in the Eurocleft and Americleft studies which had less favourable outcomes. Those with CBCLP are inferior to those reported elsewhere. Continued monitoring will allow for tracking of improvement in outcomes.

Treatment-associated changes in malocclusion and oral health-related quality of life: A 4-year cohort study.

INTRODUCTION: The impact of orthodontic treatment on oral health-related quality of life (OHRQoL) in adolescents being treated in orthodontic practices has not yet been explored longitudinally. The aim of this cohort study was to describe the changes in both malocclusion and OHRQoL with orthodontic treatment. METHODS: One hundred seventy-four patients (ages, 10-17 years; 64.4% girls; 81.6% European) underwent 2-arch, fixed-appliance treatment in a 4-year prospective study conducted across 19 specialist orthodontic practices throughout New Zealand. They were assessed before treatment, at debond (when 87.4% of the baseline sample were reassessed), and at a mean 21 months postdebond (when 59.4% of the baseline sample were reassessed). OHRQoL was measured using the Child Perceptions Questionnaire, and the Dental Aesthetic Index was used to measure occlusion. RESULTS: Among the 104 patients who took part in all 3 assessments, little change in OHRQoL overall was seen at the end of treatment, despite considerable improvement in malocclusion (with the mean Dental Aesthetic Index score falling from 35.9 at baseline to 21.3 at debond). The mean Child Perceptions Questionnaire 11-14 was slightly greater at debond, and this was most notable in the functional limitations subscale. By the end of the study (21 months postdebond, on average), the decreases in Child Perceptions Questionnaire 11-14 scores were all substantial, especially in the emotional well-being and social well-being subscales. CONCLUSIONS: Malocclusion affects orthodontic patients' OHRQoL before treatment. A temporary increase in symptomatic impacts seen by the debond stage appears to ameliorate with time, with the benefits of orthodontic treatment for OHRQoL manifesting themselves some months later.

Negative frequency-dependent interactions can underlie phenotypic heterogeneity in a clonal microbial population.

Genetically identical cells in microbial populations often exhibit a remarkable degree of phenotypic heterogeneity even in homogenous environments. Such heterogeneity is commonly thought to represent a bet-hedging strategy against environmental uncertainty. However, evolutionary game theory predicts that phenotypic heterogeneity may also be a response to negative frequency-dependent interactions that favor rare phenotypes over common ones. Here we provide experimental evidence for this alternative explanation in the context of the well-studied yeast GAL network. In an environment containing the two sugars glucose and galactose, the yeast GAL network displays stochastic bimodal activation. We show that in this mixed sugar environment, GAL-ON and GAL-OFF phenotypes can each invade the opposite phenotype when rare and that there exists a resulting stable mix of phenotypes. Consistent with theoretical predictions, the resulting stable mix of phenotypes is not necessarily optimal for population growth. We find that the wild-type mixed strategist GAL network can invade populations of both pure strategists while remaining uninvasible by either. Lastly, using laboratory evolution we show that this mixed resource environment can directly drive the de novo evolution of clonal phenotypic heterogeneity from a pure strategist population. Taken together, our results provide experimental evidence that negative frequency-dependent interactions can underlie the phenotypic heterogeneity found in clonal microbial populations.

Perinatal/Neonatal case presentation: pulmonary artery sling associated with respiratory distress.

Pulmonary artery sling is a very rare cause of pediatric respiratory distress. The estimated prevalence of the disease was first determined by Yu et al. in 2008 as 59 per million school-aged children. Associated symptoms are cough, wheezing, and feeding difficulty, all of which are common in routine outpatient pediatric clinical encounters. We report a case of a premature male neonate twin who was admitted to the neonatal intensive care unit with respiratory distress and pneumothorax. His presentation, as well as the etiology of his pulmonary disease, was felt to be consistent with those of numerous other premature infants. Akin to this was his delayed discharge on account of his slow progress with oral feeding. Parents gave a history of tachypnea and feeding difficulty to his doctors. He presented twice to the emergency room in respiratory distress. At 4 months of age, while in hospital for a pulmonary infection, he had an echocardiogram that revealed a pulmonary artery sling. We review the literature on this vascular anomaly, discuss its diagnosis and management, and critique the clinical thinking that determined this child's course from the perspective of availability heuristics.

The socio-demographic and malocclusion characteristics of adolescents presenting for specialist orthodontic treatment in New Zealand practices.

BACKGROUND: There are few reports of the socio-demographic and malocclusion characteristics of those undergoing clinical orthodontic treatment in private specialist practice. AIM: To describe the pretreatment characteristics of individuals presenting for orthodontic treatment. METHODS: Individuals (N = 174) presenting for orthodontic treatment in 19 private specialist orthodontic practices in New Zealand were randomly selected and examined (at the beginning of a three-year prospective study) and their malocclusions compared using the Dental Aesthetic Index (DAI). RESULTS: The mean DAI score was 35.8 (SD 8.4). There were no statistically significant socio-demographic differences in DAI score other than by household-based socio-economic status (SES), whereby mean scores were considerably higher in those of low SES. The majority of patients attending for treatment had severe or very severe/handicapping malocclusions. Females had less severe malocclusions than males, on average, although the difference was not statistically significant. CONCLUSIONS: The malocclusion severity threshold for seeking orthodontic treatment appears to be higher in those of lower SES. The study findings highlight the need to improve access to orthodontic treatment for this group.

A comparison between phone-based psychotherapy with and without text messaging support in between sessions for crisis patients.

BACKGROUND: Few studies have tested whether individually tailored text messaging interventions have an effect on clinical outcomes when used to supplement traditional psychotherapy. This is despite the potential to improve outcomes through symptom monitoring, prompts for between-session activities, and psychoeducation. OBJECTIVE: The intent of the study was to explore the use of individually tailored between-session text messaging, or short message service (SMS), as an adjunct to telephone-based psychotherapy for consumers who present to the Emergency Department (ED) in situational and/or emotional crises. METHODS: Over a 4-month period, two therapists offered 68 prospective consumers of a telephone-based psychotherapy service individually tailored between-session text messaging alongside their telephone-based psychotherapy. Attendance and clinical outcomes (depression, anxiety, functional impairment) of those receiving messages were compared against a historical control group (n=157) who received telephone psychotherapy only. RESULTS: A total of 66% (45/68) of the consumers offered SMS accepted the intervention. A total of 432 messages were sent over the course of the trial, the majority involving some kind of psychoeducation or reminders to engage in therapy goals. There were no significant differences in clinical outcomes between consumers who received the SMS and those in the control group. There was a trend for participants in the intervention group to attend fewer sessions than those in the control group (mean 3.7, SD 1.9 vs mean 4.4, SD 2.3). CONCLUSIONS: Both groups showed significant improvement over time. Individually tailored SMS were not found to improve clinical outcomes in consumers receiving telephone-based psychotherapy, but the study was underpowered, given the effect sizes noted and the significance level chosen. Given the ease of implementation and positive feedback from therapists and clients, individually tailored text messages should be explored further in future trials with a focus on enhancing the clinical impact of the tailored text messages, and utilizing designs with additional power to test for between-group effects.

The IAPT@Flinders Service: adapting the Improving Access to Psychological Therapies model to the emergency department setting in Australia.

OBJECTIVE: To describe the implementation of an Improving Access to Psychological Therapies (IAPT) service at Flinders Medical Centre emergency department (IAPT@Flinders). IAPT, a population-based model of guided self-help for anxiety and depression delivered mainly by phone, was rolled-out nationally in the UK in 2010. There is a growing body of evidence demonstrating its clinical effectiveness and efficiency that can improve treatment adherence, reduce stigma, remove appointment attendance barriers and improve access for hard-to-reach populations. CONCLUSIONS: IAPT@Flinders was the test site for the first IAPT in Australia and also the first IAPT service that was integrated with an emergency department (ED). IAPT@Flinders offers rapid access, low-intensity cognitive behavioural therapy, social prescribing and signposting to clients with adjustment disorders, anxiety and/or depressive symptoms. Successful implementation within an Australian crisis setting has demonstrated that many IAPT structures and protocols are applicable to ED settings and the model can be implemented with fidelity. Adaption required consideration of positioning of the service within the Australian mental health framework; staff qualifications; the referral pathways; and exclusion criteria. It is recommended additional test sites and larger scale trials are conducted to provide further evidence of the applicability of large-scale adoption of the UK IAPT model into Australian ED settings.