Graduated elastic compression stockings in the prevention of post-thrombotic syndrome: A systematic review and meta-analysis.

BACKGROUND: The effect of graduated elastic compression stockings (ECS) in the prevention of post-thrombotic syndrome (PTS) has been questioned since a large randomized trial found no prophylactic effect of ECS. OBJECTIVE: To assess the effect of the wearing time of ECS on the incidence of post-thrombotic syndrome (PTS) after proximal deep venous thrombosis, we performed a meta-analysis of the incidence of PTS across randomized and observational studies. METHOD: PubMed, Embase and Cochrane databases were searched until 12 June 2023 for studies on the effect of ECS on PTS. References of eligible studies were also screened in order to identify other potential studies that might have been missed during the search. RESULTS: Four studies comprising a total of 1467 patients met our inclusion criteria for early initiation and consistent use of ECS in patients with acute proximal DVT. ECS significantly reduced the incidence of mild-moderate PTS (OR: 0.48; 95% CI: 0.36-0.63) as well as severe PTS (OR: 0.44; 95% CI: 0.28-0.58).

Metalated Nucleic Acid Nanostructures.

Nucleic acid nanotechnology takes advantage of the self-assembling property of nucleic acids to form a variety of shapes and structures. The incorporation of metal ions into these structures introduces functionality for sensor and molecular electronic applications. Here, we describe a protocol for the incorporation of silver ions into polygonal nanoshapes that self-assemble from RNA and DNA modules.

Use of Therapeutic Drug Monitoring in Amiodarone Treatment: A Systematic Review of Recent Literature.

BACKGROUND: Amiodarone is a class III antiarrhythmic drug used to prevent supraventricular and ventricular tachyarrhythmias. It has substantial toxicity; however, the use of therapeutic drug monitoring (TDM) seems unclear in the absence of a therapeutic range or an association between amiodarone blood concentration and effect. In this review, the authors examined the reported amiodarone blood concentration measurements in the last 10 years and subsequently noted the frequency by which TDM was used to optimize therapy. METHODS: In March 2022, the Embase and MEDLINE databases were searched for articles published in English in the previous 10 years using the keywords "amiodarone," "therapeutic drug monitoring," or "serum/plasma/blood". RESULTS: This study included 19 of the 478 articles identified. TDM has not been studied in conjunction with regular amiodarone maintenance therapy. One study used TDM during the initial treatment phase but the amiodarone dose was not changed. In 3 other case reports, TDM was used to guide amiodarone treatment through drug-drug interactions, and plasma levels of the active metabolite mono-N-desethyl-amiodarone (MDEA) verified 2 amiodarone toxicities. CONCLUSIONS: Because the antiarrhythmic effect of amiodarone is not correlated with blood concentrations and is easily detectable by electrocardiogram, the routine use of TDM in maintenance therapy is controversial, as evidenced by a scarcity of published literature in the recent decade. Furthermore, amiodarone toxicity is evident with normal/low amiodarone or MDEA levels; hence, TDM of amiodarone provides no therapeutic benefit to patients.

Sonification enables continuous surveillance of the ST segment in the electrocardiogram.

INTRODUCTION: ST segment elevation myocardial infarction is a common reason for out-of-hospital cardiac arrest in adult patients. The surveillance of the ST segment in the electrocardiogram is limited to visual presentation. However, the ST segment can change during the course of treatment. If ST elevation is present immediate coronary revascularization is needed, therefore detecting ST elevation changes the treatment fundamentally. Sonification of the ST segment is a new method which enables the emergency team to detect intermediate changes of the ST segment. MATERIAL AND METHODS: We have chosen two sonification designs which were introduced to two groups, medical students and computer science students. Twenty-one participants took part in the study. The sonification was designed for evaluation of the ST segment. The user was supposed to become empowered to distinguish between no, medium-low, medium-high or extreme ST elevation by listening to the sonification. The two groups were asked to evaluate the sounds for possible ST elevation as well as for aesthetics and usability. In a second study twenty-five medical students were taking part in a medical scenario in which sonification was played during a simulated case. The patient was suffering from a myocardial infarction, ST elevation was transient and sonification sounds were changing appropriately. The students were supposed to detect these changes and act accordingly by modifying the treatment. RESULTS: Both groups were able to classify ST segment elevation by listening to the sonification samples. The higher the ST segment, the better was the detection rate overall. In all of the three categories (pleasantness, informativeness and long-term listening) the Water Ambience sonification was rated higher compared to the Polarity sonification. Moreover, in the two groups that took part in the study, we found a significant difference when comparing classification performance using both sonification designs. For the group of medical students as t(20) = 4.31, p = 3.44 × 10-4, p < 0.01 and for the computer science students as t(19) = 3.40, p = 9.39 × 10-6, p < 0.01. In the simulated medical scenario participants indicated that 96% detected the ST elevation. 60% stated that sonification played a role whereas for 32% it did not play a role for the detection of ST elevation. CONCLUSIONS: Sonification has the potential to play an important role as a new supporting tool for the surveillance of the ST segment during the care of patients with suspicion of myocardial infarction. It can be helpful to differentiate between ST segment elevation myocardial infarction and non-ST segment myocardial infarction especially if ST elevation is transient. Furthermore, sonification is viewed as pleasant to listen to and might not contribute to alarm fatigue.

A simple screening strategy for complex RNA-DNA hybrid nanoshapes.

The design of hybrid nucleic acid nanomaterials capitalizes on the partitioning of architectural and functional roles between structurally diverse RNA modules and chemically robust DNA components. Selecting optimal combinations of RNA and DNA building blocks is the key to preparing stable polygonal RNA-DNA hybrid nanoshapes. Here, we outline a simple screening strategy by gel electrophoresis under native folding conditions to identify combinations of RNA and DNA modules that self-assemble to robust polygonal hybrid nanoshapes. As a proof of concept, we outline the preparation of RNA-DNA hybrid nanoshapes containing a set of different RNA architectural joints, including internal loop motifs and three-way junction (3WJ) folds. For each hybrid nanoshape, we demonstrate the selection process used to identify optimal DNA modules from a library of DNA connectors. The simple screening strategy outlined here provides a general robust method to identify and prepare RNA-DNA hybrid nanoshapes from diverse libraries of discrete nucleic acid building blocks.

[Perioperative heparin bridging is rarely indicated].

Numerous studies have shown that perioperative heparin bridging in patients treated with a vitamin K antagonist leads to an increased incidence of bleeding and so far, there is no evidence that it leads to a significant reduction in postoperative thromboembolism as summarised in this review. Prophylactic dosage of heparin is recommended after major surgery. Heparin bridging is not relevant in patients receiving a direct oral anticoagulant due to the rapid onset and offset of action of DOACs.

Different Patterns of Attention Modulation in Early N140 and Late P300 sERPs Following Ipsilateral vs. Contralateral Stimulation at the Fingers and Cheeks.

Intra-hemispheric interference has been often observed when body parts with neighboring representations within the same hemisphere are stimulated. However, patterns of interference in early and late somatosensory processing stages due to the stimulation of different body parts have not been explored. Here, we explore functional similarities and differences between attention modulation of the somatosensory N140 and P300 elicited at the fingers vs. cheeks. In an active oddball paradigm, 22 participants received vibrotactile intensity deviant stimulation either ipsilateral (within-hemisphere) or contralateral (between-hemisphere) at the fingers or cheeks. The ipsilateral deviant always covered a larger area of skin than the contralateral deviant. Overall, both N140 and P300 amplitudes were higher following stimulation at the cheek and N140 topographies differed between fingers and cheek stimulation. For the N140, results showed higher deviant ERP amplitudes following contralateral than ipsilateral stimulation, regardless of the stimulated body part. N140 peak latency differed between stimulated body parts with shorter latencies for the stimulation at the fingers. Regarding P300 amplitudes, contralateral deviant stimulation at the fingers replicated the N140 pattern, showing higher responses and shorter latencies than ipsilateral stimulation at the fingers. For the stimulation at the cheeks, ipsilateral deviants elicited higher P300 amplitudes and longer latencies than contralateral ones. These findings indicate that at the fingers ipsilateral deviant stimulation leads to intra-hemispheric interference, with significantly smaller ERP amplitudes than in contralateral stimulation, both at early and late processing stages. By contrast, at the cheeks, intra-hemispheric interference is selective for early processing stages. Therefore, the mechanisms of intra-hemispheric processing differ from inter-hemispheric ones and the pattern of intra-hemispheric interference in early and late processing stages is body-part specific.

RNA-DNA Hybrid Nanoshape Synthesis by Facile Module Exchange.

The preparation of nucleic acid nanostructures has relied predominantly on procedures of additive fabrication in which complex architectures are assembled by concerted self-assembly and sequential addition of building blocks. We had previously established RNA-DNA hybrid nanoshapes with modular architectures that enable multistep synthetic approaches inspired by organic molecular synthesis where additive and transformative steps are used to prepare complex molecular architectures. We report the establishment of module replacement and strand exchange as synthetic transformations in nucleic acid hybrid nanoshapes, which are enabled by minimally destabilizing sequence elements such as a single unpaired overhang nucleotide or a mismatch base pair. Module exchange facilitated by thermodynamic lability triggers adds a powerful transformative approach to the repertoire of additive and transformative synthetic methods for the preparation of complex composite materials.

Determination of Face and Content Validity of Cadaveric Model for Holmium Anatomic Endoscopic Enucleation of the Prostate Training: An ESUT AEEP Group Study.

BACKGROUND: Bench and virtual reality nonbiological simulator models for anatomic endoscopic enucleation of the prostate (AEEP) surgery have been reported in the literature. These models are acceptable but have limited practical applications. OBJECTIVE: To validate a fresh-frozen human cadaver model for holmium AEEP training and assess its content validity. DESIGN SETTING AND PARTICIPANTS: Holmium AEEP operations on fresh-frozen cadavers performed by an experienced surgeon were recorded, and a video, including the main steps of the operation, was produced. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The video and an accompanying questionnaire were subsequently distributed electronically to ESUT AEEP study group experts and associates (N = 32) for assessment of the AEEP training model. A ten-point Likert global rating scale was used to measure the content validity. RESULTS AND LIMITATIONS: A total of 26 answers were returned (81%). The experts agreed on the model's suitability for AEEP training (mean Likert score: 8). According to the responses, "identifying anatomic structures and landmarks" was the most valuable aspect of the model in terms of AEEP training (median Likert score: 9). Conversely, the experts found the model's ability, in terms of demonstrating laser and tissue reactions, to be weak (median Likert score: 6). CONCLUSIONS: Based on the content validity assessment, the fresh-frozen cadaver-training model for laser AEEP seems to be a promising model for demonstrating and learning the correct prostate enucleation technique. PATIENT SUMMARY: An increasing number of researchers have proposed that anatomic endoscopic enucleation of the prostate (AEEP) should replace transurethral resection of the prostate surgery and become the gold standard for treatment of bladder outlet obstruction due to benign prostatic hyperplasia. AEEP requires anatomic familiarity for enucleation, technical knowledge, and a solid training program before starting with the first cases. This is the first cadaver study to assess the content validity of a fresh-frozen human cadaver model for AEEP training.

Nano-sandwich composite by kinetic trapping assembly from protein and nucleic acid.

Design and preparation of layered composite materials alternating between nucleic acids and proteins has been elusive due to limitations in occurrence and geometry of interaction sites in natural biomolecules. We report the design and kinetically controlled stepwise synthesis of a nano-sandwich composite by programmed noncovalent association of protein, DNA and RNA modules. A homo-tetramer protein core was introduced to control the self-assembly and precise positioning of two RNA-DNA hybrid nanotriangles in a co-parallel sandwich arrangement. Kinetically favored self-assembly of the circularly closed nanostructures at the protein was driven by the intrinsic fast folding ability of RNA corner modules which were added to precursor complex of DNA bound to the protein. The 3D architecture of this first synthetic protein-RNA-DNA complex was confirmed by fluorescence labeling and cryo-electron microscopy studies. The synthesis strategy for the nano-sandwich composite provides a general blueprint for controlled noncovalent assembly of complex supramolecular architectures from protein, DNA and RNA components, which expand the design repertoire for bottom-up preparation of layered biomaterials.

Psychological care in children and adolescents with type 1 diabetes in a real-world setting and associations with metabolic control.

BACKGROUND: International guidelines recommend psychosocial care for children and adolescents with type 1 diabetes. OBJECTIVE: To assess psychological care in children and adolescents with type 1 diabetes in a real-world setting and to evaluate associations with metabolic outcome. METHODS: Delivery of psychological care, HbA1c, and rates of severe hypoglycemia and diabetic ketoacidosis (DKA) in children and adolescents with type 1 diabetes from 199 diabetes care centers participating in the German diabetes survey (DPV) were analyzed. RESULTS: Overall, 12 326 out of 31 861 children with type 1 diabetes were supported by short-term or continued psychological care (CPC). Children with psychological care had higher HbA1c (8.0% vs 7.7%, P<.001) and higher rates of DKA (0.032 vs 0.021 per patient-year, P<.001) compared with children without psychological care. In age-, sex-, diabetes duration-, and migratory background-matched children, HbA1c stayed stable in children supported by CPC during follow-up (HbA1c 8.5% one year before psychological care started vs 8.4% after two years, P = 1.0), whereas HbA1c was lower but increased significantly by 0.3% in children without psychological care (HbA1c 7.5% vs 7.8% after two years, P <.001). Additional HbA1c-matching showed that the change in HbA1c during follow-up was not different between the groups, but the percentage of children with severe hypoglycemia decreased from 16.3% to 10.7% in children receiving CPC compared with children without psychological care (5.5% to 5.8%, P =.009). CONCLUSIONS: In this real-world setting, psychological care was provided to children with higher HbA1c levels. CPC was associated with stable glycemic control and less frequent severe hypoglycemia during follow-up.

RNA-DNA hybrid nanoshapes that self-assemble dependent on ligand binding.

Self-assembly of nucleic acid nanostructures is driven by selective association of oligonucleotide modules through base pairing between complementary sequences. Herein, we report the development of RNA-DNA hybrid nanoshapes that conditionally assemble under the control of an adenosine ligand. The design concept for the nanoshapes relies on ligand-dependent stabilization of DNA aptamers that serve as connectors between marginally stable RNA corner modules. Ligand-dependent RNA-DNA nanoshapes self-assemble in an all-or-nothing process by coupling adenosine binding to the formation of circularly closed structures which are stabilized through continuous base stacking in the resulting polygons. By screening combinations of various DNA aptamer constructs with RNA corner modules for the formation of stable complexes, we identified adenosine-dependent nanosquares whose shape was confirmed by atomic force microscopy. As a proof-of-concept for sensor applications, adenosine-responsive FRET-active nanosquares were obtained by dye conjugation of the DNA aptamer components.

Inpatient Rehabilitation for Children and Adolescents With Diabetes in Germany Between 2006 and 2013.

INTRODUCTION: In Germany, inpatient rehabilitation is a well-established additive option in the therapeutic concept for children and adolescents with diabetes. However, its contribution in pediatric diabetes care is not known exactly. Our objective was to analyze inpatient rehabilitation in pediatric diabetes over eight years in Germany. METHODS: We requested secondary data from the German Statutory Pension Insurance Scheme to evaluate all completed inpatient rehabilitations for children and adolescents with diabetes (ICD-code E10-14) reimbursed by this institution between 2006 and 2013. For each type of diabetes, we analyzed the distribution of admissions by year, age-group, sex, nationality, and other documented diagnoses. All analyses were conducted via remote computing with IBM SPSS Version 24. RESULTS: Between 2006 and 2013, 5,403 admissions to inpatient rehabilitation for 4,746 children and adolescents with diabetes were documented. For type 1 diabetes (T1D; 88.5% of admissions), the number of yearly admissions increased from 458 in 2006 to 688 in 2013 (p=0.013), especially for age-group>5-10. The increase for type 2 diabetes (T2D) was not significant. Admissions were more frequent for girls (53.6%, p≤0.001), age>10-15 years (42.8%, p=0.001), and German nationality (98.5%). Obesity (T1D: 11.1%; T2D: 87.9%) and mental disorders (T1D: 11.6%; T2D: 27.4%) were the most frequent documented diagnoses in addition to diabetes. CONCLUSION: This study provides a comprehensive overview of inpatient rehabilitation for children and adolescents with diabetes over many years in Germany. Until 2013, inpatient rehabilitation remained important in pediatric diabetes care, especially for children with mental disorders or obesity.

Rehabilitation in Germany 2004-2016 A Multicenter Analysis Over a Period of 13 Years in Children and Adolescents with Diabetes Mellitus.

In the treatment of children/adolescents with diabetes medical rehabilitation plays an important role. It was the aim of the survey to analyze trends in the number of patients admitted to rehabilitation, the quality of diabetes care, the incidence of acute complications, risk factors for cardiovascular co-morbidities like lipids and blood pressure and the familial status nationwide and over a period of 13 years. METHODS: Currently seven hospitals offer in-patient rehabilitation for children/adolescents with diabetes in Germany. Six hospitals participated in the survey. All children/adolescents (n=7.163) who participated in an in-patient rehabilitation 01/01/2004-31/12/2016 were included. Clinical/familial data were assessed: age, sex, family situation, type/duration of diabetes, insulin dosage, self-monitoring, acute complications, height, body weight, blood pressure and laboratory parameters. For collecting and storage of data the computer software DPV® (Diabetes-Patienten-Verlaufsdokumentation, University of Ulm, Germany) was used. Statistical analyses were performed using the programme SAS (Statistical Analysis Software 9.4, SAS Institute Inc, Cary, North Carolina, USA). RESULTS: During the study period 7.163 patients took part in 10.987 in-patient rehabilitation procedures. The yearly number of patients participating in rehabilitation remained stable. There was no change in the quality of diabetes control (HbA1c: p=0.30, fasting blood glucose: p=0.80). The incidence of severe hypoglycaemia decreased (p<0.001). The incidence of ketacidosis remained stable (p=0.18). The frequency of blood glucose self-monitoring increased (p<0.001). The same was true for patients treated with CSII (p<0.001), whereas the numbers of patients treated with CT or ICT decreased (both p<0.001). There was no change in patients' total insulin dose (p=0.01). There was a decrease of the number of patients living with both parents (p<0.001), the percentage of children/adolescents living with mother or father alone increased (p<0.001). The percentage of children/adolescents living in mixed cultural families or having a background of immigration increased (p<0.001). CONCLUSIONS: There is a change in medical rehabilitation: The number is stable, the proportion of patients using CSII increased, the number of patients living with single parents and the percentage of patients from culturally mixed families increased also.

A pan-Canadian measure of active living environments using open data.

BACKGROUND: Neighbourhood environments that support active living, such as walking or cycling for transportation, may decrease the burden of chronic conditions related to sedentary behaviour. Many measures exist to summarize features of communities that support active living, but few are pan-Canadian and none use open data sources that can be widely shared. This study reports the development and validation of a novel set of indicators of active living environments using open data that can be linked to national health surveys and can be used by local, regional or national governments for public health surveillance. DATA AND METHODS: A Geographic Information System (GIS) was used to calculate a variety of measures of the connectivity, density and proximity to destinations for 56,589 dissemination areas (DAs) across Canada (2016 data). Pearson correlation coefficients were calculated to assess the association between each measure and the rates of walking to work and taking active transportation to work (a combination of walking, cycling and using public transportation) from census data. The active living environment measures selected for the final database were used to classify the DAs by the favourability of their active living environment into groups by k-medians clustering. RESULTS: All measures were correlated with walking-to-work and active-transportation-to-work rates at the DA level, whether they were derived using proprietary or open data sources. Coverage of open data was consistent across Canadian regions. Three measures were selected for the Canadian Active Living Environments (Can-ALE) dataset based on the correlation analysis, but also on the principles of suitability for a variety of community sizes and openly available data: (1) three-way intersection density of roads and footpaths derived from OpenStreetMap (OSM), (2) weighted dwelling density derived from Statistics Canada dwelling counts and (3) points of interest derived from OSM. A measure of access to public transportation was added for the subset of DAs in larger urban areas and was strongly related to active-transportation-to-work rates. Active-transportation-to-work rates were graded, in steps, by the five Can-ALE groups derived from the cluster analysis, although walking-to-work rates exceeded the national average only in the most favourable active living environments. DISCUSSION: Open data may be used to derive measures that characterize the active living environments of Canadian communities.

Pentadiynylidene and Its Methyl-Substituted Derivates: Threshold Photoelectron Spectroscopy of R1-C5-R2 Triplet Carbon Chains.

Mass-selective threshold photoelectron spectroscopy in the gas phase was employed to characterize the dialkynyl triplet carbenes pentadiynylidene (HC5H), methylpentadiynylidene (MeC5H), and dimethylpentadiynylidene (MeC5Me). Diazo compounds were employed as precursors to generate the carbenes by flash pyrolysis. The R1-C5-R2 carbon chains were photoionized by vacuum ultraviolet (VUV) synchrotron radiation in photoelectron photoion coincidence (PEPICO) experiments. High-level ab initio computations were carried out to support the interpretation of the experiments. For the unsubstituted pentadiynylidene (R1 = R2 = H) the recorded spectrum yields an adiabatic ionization energy (IEad) of 8.36 ± 0.03 eV. In addition, a second carbene isomer, 3-(didehydrovinylidene)cyclopropene, with a singlet electronic ground state, was identified in the spectrum based on the IEad of 8.60 ± 0.03 eV and Franck-Condon simulations. We found that multireference computations are required to reliably calculate the IEad for this molecule. CASPT2 computations predicted an IEad = 8.55 eV, while coupled-cluster computations significantly overestimate the IE. The cyclic isomer is most likely formed from another isomer of the precursor present in the sample. Stepwise methyl-substitution of the carbene leads to a reduction of the IE to 7.77 ± 0.04 eV for methylpentadiynylidene and 7.27 ± 0.06 eV for dimethylpentadiynylidene. The photoionization and dissociative photoionization of the precursors is investigated as well.

The effect of DPP-4-protected GLP-1 (7-36) on coronary microvascular function in obese adults.

OBJECTIVE: Glucagon-like-peptide-1 (GLP-1) receptor analogues have been shown to reduce cardiovascular events in patients with type 2 diabetes. However, the mechanism behind is still unknown. The aim of the study was to investigate the effect of intact GLP-1 (7-36) on coronary microcirculation in overweight adults. DESIGN AND METHODS: A double-blinded randomized cross-over study was performed, with 12 overweight participants. Effects of intact GLP-1 (7-36) infusion were compared with a saline infusion on separate days. A DPP-4 inhibitor was administered to block degradation of intact GLP-1 (7-36) to the GLP-1 metabolite (9-36). Coronary microcirculation was assessed by Doppler coronary flow velocity reserve (CFVR) before and after 2 h of infusion. Peripheral endothelial function was assessed by flow mediated dilation (FMD) before and after one hour of infusion. RESULTS: CFVR was 3.77 ±â€¯1.25 during GLP-1 infusion and 3.85 ±â€¯1.32 during saline infusion, endothelial function was 16.3 ±â€¯15.5 % during GLP-1 infusion and 7.85 ±â€¯7.76 % during saline infusion. When adjusting for baseline values no significant differences in CFVR (ΔCFVR 0.38 ±â€¯0.92 vs. ΔCFVR 0.71 ±â€¯1.03, p = 0.43) and no difference in peripheral endothelial function (ΔFMD 7.34 ±â€¯11.5 % vs. ΔFMD -1.25 ±â€¯9.23%, p = 0.14) was found. CONCLUSIONS: We found no effect of intact GLP-1 (7-36), protected from DPP4 mediated degradation on coronary microcirculation in overweight adults.

Versatile kit of robust nanoshapes self-assembling from RNA and DNA modules.

DNA and RNA have emerged as a material for nanotechnology applications that take advantage of the nucleic acids' ability to encode folding and programmable self-assembly through mainly base pairing. The two types of nucleic acid have rarely been used in combination to enhance structural diversity or for partitioning of functional and architectural roles. Here, we report a design and screening strategy to integrate combinations of RNA motifs as architectural joints and DNA building blocks as functional modules for programmable self-assembly of a versatile toolkit of polygonal nucleic acid nanoshapes. Clean incorporation of diverse DNA modules with various topologies attest to the extraordinary robustness of the RNA-DNA hybrid framework. The design and screening strategy enables systematic development of RNA-DNA hybrid nanoshapes as programmable platforms for applications in molecular recognition, sensor and catalyst development as well as protein interaction studies.

Prediction of obstructive coronary artery disease and prognosis in patients with suspected stable angina.

AIMS: We hypothesized that the modified Diamond-Forrester (D-F) prediction model overestimates probability of coronary artery disease (CAD). The aim of this study was to update the prediction model based on pre-test information and assess the model's performance in predicting prognosis in an unselected, contemporary population suspected of angina. METHODS AND RESULTS: We included 3903 consecutive patients free of CAD and heart failure and suspected of angina, who were referred to a single centre for assessment in 2012-15. Obstructive CAD was defined from invasive angiography as lesion requiring revascularization, >70% stenosis or fractional flow reserve <0.8. Patients were followed (mean follow-up 33 months) for myocardial infarction, unstable angina, heart failure, stroke, and death. The updated D-F prediction model overestimated probability considerably: mean pre-test probability was 31.4%, while only 274 (7%) were diagnosed with obstructive CAD. A basic prediction model with age, gender, and symptoms demonstrated good discrimination with C-statistics of 0.86 (95% CI 0.84-0.88), while a clinical prediction model adding diabetes, family history, and dyslipidaemia slightly improved the C-statistic to 0.88 (0.86-0.90) (P for difference between models <0.0001). Quartiles of probability of CAD from the clinical prediction model provided good diagnostic and prognostic stratification: in the lowest quartiles there were no cases of obstructive CAD and cumulative risk of the composite endpoint was less than 3% at 2 years. CONCLUSION: The pre-test probability model recommended in current ESC guidelines substantially overestimates likelihood of CAD when applied to a contemporary, unselected, all-comer population. We provide an updated prediction model that identifies subgroups with low likelihood of obstructive CAD and good prognosis in which non-invasive testing may safely be deferred.