The TKD group had a significant delay in skeletal development at baseline compared to the control group (p = 0.003) but caught up with the controls at 3 months (p = 0.041). Improvements in the MABC scores were also seen in both groups across time (p < 0.017). Only the TKD group had a significant improvement in the EHC movement time at 3 (p = 0.009) and 6 months (p = 0.016). The adapted TKD intervention may be effective in improving the skeletal development and EHC movement time of children with DCD. For motor performance, the effect of maturation might be more profound.This study evaluated the effectiveness of adapted Taekwondo (TKD) training on skeletal development and motor performance in children with developmental coordination disorder (DCD). One hundred forty-five prepubertal children with DCD were allocated to either the TKD or control groups. Children in the TKD group participated in a weekly 1-hour adapted TKD intervention and daily TKD home exercises for 12 weeks. The primary outcome  and secondary outcomes (Movement Assessment Battery for Children (MABC) total impairment score, eye–hand coordination (EHC) scores, and a standing balance score) were measured at baseline, after the intervention and 3 months after the intervention. Skeletal development improved in both groups over time ( Children with DCD are characterized by their marked motor impairments, such as poor body balance6 and eye–hand coordination (EHC)7. These deficits in upper and lower limb movement are detrimental to the development of overall motor skills and limit participation in activities4. In particular, poor body balance, which affects 73% to 87% of children with DCD, may result in a predisposition to falls and injuries in daily life4, which is a major concern of most parents. Active alternative treatment strategies are required to remediate the motor and balance impairments in this group of children.Developmental coordination disorder (DCD) is one of the most common motor-based disorders and affects approximately 6% of children studying in primary schools8. The delay in skeletal development, which is reflected by bone age, is also associated with lower bone mineral density9 and bone mineral mass in skeletally immature individuals10. Therefore, the establishment of an active treatment program to enhance skeletal development and bone health in children with DCD is essential.In addition to motor impediment, our research team found that skeletal development is also compromised in children with DCD, which is associated with the sedentary lifestyle of these children12. Shin et al.11 reported that the bone mineral density of the lumbar spine was higher in growing, adolescent TKD athletes than in sedentary control subjects because TKD is a weight-bearing and contact sport. We hypothesized that TKD training might also facilitate skeletal development in children with DCD.Sports training is often an enjoyable and practical way to improve both motor skills and skeletal development in young people. For example, training in taekwondo  has been shown to be effective in improving bone health in young people13. In our previous studies, we found that as little as 3 months of TKD training could improve gross motor proficiency, such as single-leg standing balance control, vestibular function14, and knee muscle strength2, in children with DCD14. Although no study has yet specifically investigated the effects of TKD training on the improvement of upper limb motor performance in this group of children, we postulated that TKD exercises might enhance proficiencies such as eye–hand coordination because visual-motor training  is emphasized in TKD15. Indeed, a previous study has reported that karate  athletes had better eye-hand coordination than non-contact sports athletes16. Therefore, the aim of this study was to investigate the effectiveness of a novel adapted TKD training regimen on both skeletal development and motor proficiency, including overall motor performance, eye–hand coordination, and standing balance control, in prepubertal children with DCD.TKD is also famous with its kicking techniques, in which single-leg stance stability is crucial and is a determining factor of success in competitionsp = 0.002). Baseline physical activity level was therefore treated as a covariate in the statistical analyses. Seventeen participants in the TKD group and 31 participants in the control group dropped out of the trial  and 0.79 years at 6 months . In the control group, skeletal development improved by 0.55 years  and 0.68 years  at 3 months and 6 months, respectively. A separate statistical analysis was performed after the removal of the dropout cases, and similar results were obtained (data not shown).Table p < 0.001) and 4.79 points at 6 months . In the control group, the MABC total impairment score improved by 2.11 points  and 2.31 points  at 3 months and 6 months, respectively. No significant between-groups differences were found at all time points  and 6 months . However, the mean differences between the two groups at all time points were not significant. The EHC accuracy value and reaction time remained relatively stable in both groups across time, and none of the between-groups differences were significant. The mCTSIB composite sway index also showed no significant within-group changes or between-groups differences at any time point  in children with DCD. Continuous improvement in the EHC outcome was observed for 3 months after the cessation of training. However, adapted TKD training may not be able to improve the overall motor performance or static standing balance performance of children with DCD.12, possibly because TKD training  places a considerable amount of dynamic, high-magnitude, and high-velocity mechanical stress on growing bones  and cartilage15. These external forces may act on the skeleton to stimulate and hasten cartilage growth and chondro-osseous development17. However, the mechanisms behind the continuous improvement in skeletal development after the cessation of TKD training remain less understood. The improvement may be primarily due to maturation, as both groups demonstrated similar improvements from 3 to 6 months. Further exploration is warranted to confirm the longer-term effects of adapted TKD training on skeletal development in children with DCD.The improvement in skeletal development in the TKD group at 3 months supports our hypothesis that TKD training can facilitate skeletal development in children with DCD. Although the control group also improved over time, which suggests that the effect of maturation cannot be ignored, the improvement was greater in the TKD group (0.74 years) than in the control group (0.55 years). The TKD group had a significant delay in skeletal development at baseline compared to the control group but caught up with the control subjects at 3 months. These findings suggest that TKD training could hasten the development of bone in children with DCD and are consistent with the bone-strengthening benefit of TKD reported in previous studies18. Thus, our result reveals that training in TKD could probably shorten the biomechanical delay in generating muscle forces in the upper limbs. This finding is consistent with previous studies that suggested that martial arts athletes have better motor control and coordination of the upper limbs, which may be related to the repeated practice of martial art skills20. Our results further show that this improvement continued until 3 months after the cessation of TKD martial art training, although the underlying mechanisms are still not clear and require further research.Another encouraging finding of this study was that EHC movement time improved from baseline to 3 months and 6 months exclusively in the TKD group. EHC movement time is a measure of the biomechanical delay required to generate sufficient muscle force to complete a finger-pointing task21. Therefore, we postulate that 3 months of TKD training may not be long enough to elicit a training effect in EHC reaction time. Another plausible reason was that our reaction time test (a finger-pointing task) results could be confounded by the attention level of the participants with DCD who are known to be inattentive to motor tasks22. Therefore, further study may monitor the attention level of the participants concurrently during the EHC test23. As for the EHC accuracy value, because coordination is task specific, the gross eye–hand coordination skills  developed through TKD training may not be carried over to the static finger-pointing task, which requires fine motor control24.Although EHC movement time improved in the TKD group, EHC reaction time and accuracy did not change over time in either group. A previous study reported that TKD practitioners with more than 3 years of training had faster reaction times than control subjects in response to a visual stimulus14. Further studies may consider using dynamic balance tests such as the Star Excursion Balance Test25 to assess the dynamic and functional balance performance of children with DCD.We found that both TKD and control groups demonstrated similar overall improvements in gross and fine motor performance over time. Thus, the effect of maturation (spontaneous improvement) may be more profound than that of TKD training. With respect to static standing balance performance, surprisingly, neither group showed significant improvement over time. This could be attributable to the fact that testing static balance in a bipedal stance on a force platform was not sufficiently challenging to reflect the participants’ actual balance ability26. Second, the findings of this laboratory-based study may not be generalizable to non-laboratory environments such as outdoor or clinical settings. Further studies should examine whether the skeletal and EHC improvements in children with DCD are clinically meaningful and take individual differences into account. Third, the TKD intervention lasted for only 3 months, which may not be long enough to induce marked skeletal development. A future study could include a longer-term TKD intervention and assess the long-term effectiveness of such an intervention. Finally, ultrasonic bone age assessment may not be sensitive enough to detect minimal changes in bone growth. Biomarkers of bone growth could be examined instead.This study has some limitations. First, due to the nature of TKD intervention, the participants cannot be blinded to group assignment. The optimism of the TKD group participants about the potential benefits of the exercise intervention may have introduced some bias to the resultsThe 3-month adapted TKD program may be effective in improving skeletal development and EHC movement time in children with DCD. However, with respect to overall motor performance, the effect of maturation might be more profound than that of TKD. In addition, the TKD intervention may not be able to improve the static standing balance performance, EHC reaction time and finger-pointing accuracy of children with DCD.This prospective, randomized, single-blind and controlled trial was registered at ClinicalTrials.gov NCT02635711) on December 21, 2015 and was approved by the Human Research Ethics Committee of the University of Hong Kong (reference number: EA1501110). Written informed consent was obtained from each participant and parent, and all procedures were conducted in accordance with the Declaration of Helsinki. Figure 1 on Dece1; a gross motor composite score of 42 or less on the Bruininks-Oseretsky Test of Motor Proficiency27 or a total impairment score below the 5th percentile on the Movement Assessment Battery for Children (MABC)28; a total score of less than 46 (for children 5 to 7 years 11 months of age) or less than 55 (for children 8 to 9 years 11 months) on the DCD Questionnaire 200729; attendance at a mainstream primary school; normal intelligence; ability to follow instructions; and no experience in TKD or other martial arts. The exclusion criteria were as follows: neurological or other movement disorder; diagnosis of congenital, sensory, musculoskeletal, cardiopulmonary, or psychiatric disorder that may affect skeletal development or motor performance; active treatment such as complementary and alternative medicine that may confound the effects of the intervention; or demonstration of excessive disruptive behavior (as self-discipline is important in a TKD class)15.Children with DCD were recruited from nongovernmental organizations, primary schools, and parents’ groups through poster and online advertising and from our research team’s database of DCD study participants. The inclusion criteria were as follows: age between 6 and 9 years; Tanner stage I; diagnosis of DCD based on the Diagnostic and Statistical Manual of Mental Disorders Vwww.random.org) and sealed opaque envelopes to ensure concealed allocation.Two physiotherapists first screened the volunteers by telephone, and those who seemed eligible underwent an in-person evaluation and baseline assessment. All eligible participants were randomly assigned to either a TKD group or a control group. The randomization procedure was performed by an independent person with a computer-generated randomization sequence 15 except that our participants spent more time on striking and kicking techniques. It is because we postulated that the high-impact striking techniques  incorporated in the program might stimulate bone growth17, whereas the kicking and striking focus mitt practice might improve balance control14 and eye–hand coordination30, respectively. The TKD group attended a weekly 1-hour session of adapted TKD training that was held at the University of Hong Kong for 12 weeks. All TKD training sessions were conducted by a World Taekwondo Federation black belt coach and an assistant coach. In addition, each participant was given TKD home exercises to increase the training frequency to 7 times/week14. The home exercises were the same as those practiced during the supervised TKD sessions. Parents were required to document the child’s TKD home practice in a logbook. The active control group received no TKD training but jogged for 1 hour per day for 12 weeks in their natural environment. Pedometers were used to monitor the exercise level, and the pedometer counts (steps/day) were documented by the parents in a logbook.The participants who were assigned to the TKD group underwent an adapted TKD training regimen (detailed in Table All the participants were assessed before the start of the intervention (baseline), shortly after the 3-month intervention (post-test), and 3 months after its completion (follow-up test) by two trained research assistants who were blinded to the intervention allocation. Data collection took place in the Physical Activity Laboratory at the University of Hong Kong.31. Dietary calcium intake was estimated using the Hong Kong Hospital Authority Hong Kong East Cluster’s Nutrition Information website (http://www3.ha.org.hk/dic/nq_03.html).Age, sex, body weight, height, arm length, hand dominance, indoor and outdoor exercise habits, comorbid conditions, medical history, and treatments received were obtained from medical records, if available, and by interviewing the participants and parents. Body mass index was calculated by dividing body weight (kg) by the square of height (m). Habitual physical activity level was calculated based on the exercise intensity, duration, frequency, and the assigned metabolic equivalent (MET) value of the physical activity according to the Compendium of Energy Expenditures for Youth33. During the test, each participant rested his or her left forearm on the measurement table of the BoneAge device. The assessor helped the participant to position and stabilize the distal tip of the left ulna styloid process between the two ultrasound transducers of the device. Ultrasonic waves at 750 kHz were then transmitted through the left wrist between the two ultrasound transducers. A total of 5 to 11 cycles of measurement were performed to ensure high precision. The BonAge device calculated the speed of sound and uses the distance between the two transducers, under known and controlled pressure conditions, and a proprietary sex- and ethnicity-based algorithm to provide a numeric result of bone age33. The ‘delay in skeletal development’ was then calculated by subtracting the bone age from the participant’s chronological age8.The skeletal development of each participant was determined by ultrasonography using the Sunlight BonAge system , which provides an accurate assessment of skeletal age in children (intra-operator precision: 0.24 years for boys and 0.25 years for girls). The results obtained from this ultrasonic bone age measurement are highly correlated with the conventional Greulich and Pyle method34. The assessment comprises eight tasks for each of the four age bands . The eight tasks are divided into three domains: manual dexterity, ball skill, and static and dynamic balance. The detailed assessment items are described in Henderson and Sugden28. Each participant was assessed with the appropriate age-band tests according to their chronological age. The raw score for each test item was summed to obtain a total impairment score, which was used for analysis. A lower total impairment score represents better motor performance28.The MABC was used to assess the motor proficiency of all participants. It is a standardized, validated and reliable tool for measuring gross and fine motor performance in children between 4 and 12 years of age35. In brief, the participant’s dominant hand was placed on a force-sensing resistor  positioned 10 cm from a touch screen . Visual targets in the form of a ball (1.2 cm in diameter) appeared on the screen in a random order. The participant was instructed to touch each target with the index finger of the dominant hand as quickly and as accurately as possible. Each participant repeated this finger-pointing task 15 times. Accuracy (in mm) was defined as the absolute value of the deviation of the participant’s touch location from the center of the visual target36. The accuracy scores for each trial were recorded, and the mean accuracy score of 15 trials was used for analysis. A smaller value indicates greater accuracy. In addition, the average reaction time  and the average movement time  of the 15 trials were calculated. The test–retest reliability of this eye–hand coordination test was found to be moderate 35.Upper limb motor proficiency was assessed with a computerized eye–hand coordination test. The detailed assessment procedures are described in our previous study37. During the test, each participant stood barefoot on the force platform of a Biosway computerized dynamic posturography machine  and was exposed to four sensory conditions in order: condition 1 – eyes open and firm surface; condition 2 – eyes closed and firm surface; condition 3 – eyes open and foam surface; and condition 4 – eyes closed and foam surface. The computerized dynamic posturography machine tracked the participant’s sway angle and direction from center over the four sensory conditions and automatically generated a sway index for each condition and a composite sway index . The composite sway index, which reflects the participant’s overall static standing balance ability, was used for analysis. A smaller sway index indicates better balance performance38.Standing balance control was assessed using a modified Clinical Test of Sensory Integration and Balance (mCTSIB), which is one of the most widely used tests of balance performance in children with disabilities14, with 80% power and an alpha level of 5% (two-tailed), a minimum of 23 participants per group was required.Sample size was calculated using G*Power version 3.1.0 . Based on our pilot study, an average effect size of 0.99 was assumed for the primary outcome measure. Because a dropout rate of 25% was anticipatedt-test for continuous data and a chi-square test for categorical data. The effects of TKD on primary and secondary outcomes were compared by means of mixed-model repeated-measures analysis of covariance with adjustment for demographic  and baseline covariates. The between-subjects factor was group, and the within-subject factor was time. Post hoc tests were conducted only if the results of the analysis of covariance indicated that the null hypothesis should be rejected. Independent t-tests with 95% confidence intervals (CIs) were used to compare group means, and paired t-tests were used to examine the within-group changes from baseline to 6 months. All p values were subjected to Bonferonni adjustment to maintain an overall two-tailed significance level at 5%.Statistical analyses were performed with SPSS 24.0  and based on an intention-to-treat (last-observation-carried-forward) assumption. Descriptive statistics were produced for all of the variables. The normality of the data was checked using the Kolmogorov-Simirnov test and/or histograms. Between-groups differences in demographic and baseline outcome variables were tested with an independent


The SCOPE trials  have been the backbone of oesophageal RT trials in the UK. Many changes in oesophageal RT techniques have taken place in this time. The SCOPE trials have, in addition to adopting these new techniques, been influential in aiding centres with their implementation. We discuss the progress made through the SCOPE trials and include details of a questionnaire sent to participating centres. to establish the role that trial participation played in RT changes in their centre.Questionnaires were sent to 47 centres, 27 were returned.100% of centres stated their departmental protocol for TVD was based on the relevant SCOPE trial protocol. 4DCT use has increased from 42 to 71%. Type B planning algorithms, mandated in the NeoSCOPE trial, were used in 79.9% pre NeoSCOPE and now in 83.3%.12.5% of centres were using a stomach filling protocol pre NeoSCOPE, now risen to 50%. CBCT was mandated for IGRT in the NeoSCOPE trial. 66.7% used this routinely pre NeoSCOPE/SCOPE 2 which has risen to 87.5% in the survey.The results of the questionnaires show how participation in national oesophageal RT trials has led to the adoption of newer RT techniques in UK centres, leading to better patient care.The online version of this article (10.1186/s13014-019-1225-0) contains supplementary material, which is available to authorized users. Chemoradiotherapy (CRT) has a role in the management of potentially curable oesophageal cancer in the definitive (dCRT)  and neoaQuestionnaires were provided to 47 centres that had participated in SCOPE 1/NeoSCOPE or expressed interest in SCOPE 2. Questionnaires were first distributed to participants at the SCOPE 2 launch meeting held in April 2016 and by email to those who were unable to attend the meeting. Reminder emails were sent between April 2016 and October 2017. By this time point 27 questionnaires were returned and the results are presented here. The results were analysed by question and no additional stratification was made for entry or timeline in working towards entry. The results refer to the use of the technique in routine clinical practice, rather than specifically for trial patients. The questionnaire is available in the Additional file SCOPE 1  was a phNeoSCOPE  was a phSCOPE 2 followed on from SCOPE 1 for the definitive non-surgical management of oesophageal cancer. The trial is looking at the role of dose intensification and adaptive therapy. Through a 2 × 2 design, one randomisation examines dose escalation from 50Gy in SCOPE 1 to 60Gy, to gross tumour, delivered as simultaneous integrated boost . There iThe corresponding RT developments in each of the trials are detailed in Table There was a return rate of 57% in this study. There was good representation from departments across the UK, including the devolved nations. The results are shown in Table Variation in target volume delineation (TVD) can be a major issue for clinical trials and without clear protocol clinicians will adopt their own interpretation of target volumes . Prior thttp://www.ncri-pet.org.uk).EUS  was considered optional for the SCOPE 1   and clinical target volume (CTV) and planning target volumes (PTV). Protocols for target volume delineation, planning technique and doses to OARs were developed for all the trials. CTV and PTV margins in SCOPE 1 were based on the distance from the gross tumour volume (GTV), using a combination of manual growth and computer-generated geometric margins, but NeoSCOPE and SCOPE 2 offered the opportunity to further refine the definition of ‘tissue at risk’ encompassed in the CTV. NeoSCOPE and SCOPE 2 attempted to define areas of elective nodal irradiation (ELNI) areas as part of the CTV . For SCOMotion of the lower oesophagus/gastro-oesophageal junction primary and ELNI regions can be marked during respiration and subject to motion and deformation as a consequence of respiration, swallowing, peristalsis, gastric filling and emptying, vascular and cardiac pulsations . The useIn order to facilitate centres to undertake 4DCT in the trial, the RT protocol gave 2 options for creation of an internal target volume (ITV) with 4DCT  was developed to assist centres with implementing this technique. A 4DCT pre-accrual test case was also made available. Prior to NeoSCOPE only 10/24 (42%) of centres in our survey were using 4DCT for lower third oesophageal cases The number using 4DCT had increased to 17 (71%) by the time of the survey.A single method of ITV creation was recommended for the SCOPE 2 trial (4DCT method 1). A Royal College of Radiologists (RCR) webinar  conformal RT and this became the standard of care in many centres for oesophageal cancer. The latter led to significant improvements in terms of cardiac dose-volume criteria , 21, in et al [n = 413) and IMRT (n = 263). Compared with IMRT, 3D-CRT patients had a significantly greater risk of dying  and of locoregional recurrence (p = .0038). No difference was seen in cancer-specific mortality; however an increased cumulative incidence of cardiac death was seen in the 3D-CRT group (p = .049), suggesting IMRT should be considered for treatment of oesophageal cancer. The first planning study looking at the dosimetric benefits of IMRT for oesophageal cancer was from the Royal Marsden in 2001 . Due to et al  comparedPlanning studies from Oxford had shown that doses of RT could be escalated without exceeding doses to organs at risk when a simultaneous integrated boost to the GTV was delivered, using IMRT . SCOPE 2The choice of dose calculation algorithm for RT planning affects the accuracy of calculated.dose distributions, particularly in areas of tissue inhomogeneity such as the lungs. In heterogeneous situations, the algorithms which provide approximate modelling for the variation of penumbra with density (type b) have been shown to model the dose more accurately than those which do not (type a) when compared to Monte Carlo as a gold standard of calculation accuracy. This is of importance in oesophageal RT as it is often the case that the gross disease lies adjacent to the lung tissue . While bPrior to SCOPE 1 only 42% outlined the heart as an organ at risk (OAR) . The heaTVD with 4DCT, by taking into account internal motion, leads to individualised margins, but needs to be accompanied by rigorous quality control of treatment delivery. Two-dimensional megavoltage portal imaging is insufficient in the 4D era, where a form of volumetric imaging, such as cone-beam computed tomography (CBCT) is required , 27. CBCSCOPE 1 introduced a Radiotherapy Quality Assurance (RT QA) programme to ensure the quality of the RT delivered in the trial , as it iFor NeoSCOPE, in part due to the concerns raised about possible toxicity, there was a more rigorous QA process . An outlFor SCOPE 2, as per NeoSCOPE trial, a rigorous RTQA programme was established. There was however a move within the UK RTTQA community to reduce the burden of QA on centres by streamlining the QA process for trials as far as possible, so centres that had previously passed the pre-accrual outlining QA for NeoSCOPE were exempt from repeating the pre-accrual outlining exercise. Due to a change in planning technique we were unable to do the same for the pre-accrual planning exercise. A detailed RT protocol was again produced and subjected to an iterative development process after peer review. As with NeoSCOPE, it is expected that pre-accrual QA will be accompanied by an ‘on trial’ component with a mixture of both real time (feedback within 3 working days) and timely retrospective review (feedback within first 10 fractions of RT). Due to the number of cases within the trial real time QA will be reserved for the 1st case from each centre (+/− 1st high dose arm) of all cases treated within the trial.https://www.rcr.ac.uk/clinical-oncology/service-delivery/radiotherapy-target-definition-and-peer-review), which has drawn heavily in some aspects on the experience of trials QA in the SCOPE trials.The RTTQA process for the trials has led to the establishment of a community of practice with 2 way dialogues with centres providing a supportive, mentoring culture which has been shown to support learning . An educAccepting the limitations of the study , the results of the questionnaires support how participation in national oesophageal RT trials has led to the adoption of newer RT techniques in UK centres, leading to better patient care. These developments have been supported by a comprehensive quality assurance programme. Most importantly, it has shown that there is an enthusiastic upper gastrointestinal clinical oncology community that can successfully complete trials and deliver high-quality RT.Additional file 1:Supplementary material Questionnaire sent to centres. (DOC 27 kb)


In the experimental arm, 55.0% of the prescriptions were appropriate versus 29.4% in the control arm (Odds Ratio (OR): 3.61 (2.60 to 5.02)). Access to the first prescription support tool synthesizing the use of oral ATs for outpatients significantly improved the rate of appropriate oral AT prescriptions according to the guidelines.Ensuring the appropriateness of prescriptions of oral antithrombotics  is a crucial safety issue, particularly for patients with multiple chronic conditions. Our main objective was to assess the impact of a prescription support tool, synthesized from international guidelines on oral ATs in adult outpatients, on improving physician adherence to the guidelines for prescription of oral ATs. A web-based, open randomized controlled trial using clinical vignettes was conducted in France from November 2018 to February 2019. General practitioners and cardiologists with outpatient practice were contacted to participate in a web-based survey involving three clinical vignettes illustrating cases of adult outpatients with common neuro-cardiovascular diseases. They were asked to answer four multiple-choice questions related to the number of oral AT(s), drug class, dosage and duration of the prescription. Physicians assigned to the experimental arm had access to the prescription support tool. Physicians assigned to the control arm had no access to the tool. The primary outcome measure was the appropriate prescription of oral ATs . An intent-to-treat analysis was performed using a logistic mixed model with a clinical vignette effect and a physician effect nested in the arm of the trial. Four hundred and forty-one general practitioners and 37 cardiologists were randomized to the experimental ( Antithrombotics (ATs), which include antiplatelet and anticoagulant therapies, are the most frequent drug class implicated in serious and fatal adverse drug events (ADEs) occurring in outpatient settings —among whSeveral studies have reported the inappropriate use of oral ATs in patients with non-valvular atrial fibrillation  ,6,7,8. RHowever, ensuring the appropriateness of prescriptions of oral ATs, especially oral AT combinations, is a crucial safety issue, particularly for patients with multiple chronic conditions. We previously showed that international guidelines on oral AT combinations were numerous, although consensual, frequently updated, and that none encompassed all the clinical situations . We hypoIn this current study, we aimed to assess the impact of this prescription support tool on improving physician adherence to the guidelines for prescription of oral ATs .The full protocol has been previously published . No chanAn open randomized controlled trial was performed in France by using an online survey targeting physicians managing outpatients with oral ATs. To measure the effect of the prescription support tool, we used clinical vignettes, a method previously shown to be effective to evaluate the quality of care ,13. The This trial was conducted among French general practitioners and cardiologists identified and contacted by email via physician associations, social networks or a snowball effect. Physicians were asked to answer an exhaustive questionnaire including their characteristics, their degree of self-confidence in prescribing oral AT combinations, their knowledge on the most recent guidelines and where to find them. Physicians with an exclusive hospital practice were not eligible to participate to the trial.Eligible physicians were allocated to the experimental arm (access to the prescription support tool) or to the control arm (no access to the prescription support tool) by randomization (1:1 ratio) with a computer-generated randomization scheme in blocks of 4, stratified by medical specialty . Randomization was centralized through the online survey.2DS2VASc and HAS BLED scores . It. It10]. D scores ,17.All physicians in both arms had access to the internet and therefore to all available material .Physicians were asked to propose prescriptions for three clinical vignettes illustrating common outpatient clinical situations. For each clinical vignette, multiple-choice questions on the number of oral ATs, drug class of oral ATs, dosage of each oral AT prescribed, and duration of the prescription were proposed. The clinical vignettes were previously created by two physicians (1 cardiologist and 1 internist-geriatrician) in order to cover the common outpatient clinical situations for which the use of oral ATs  is recommended or needs to be stopped according to the guidelines. The fifth and last question evaluated the self-reported degree of confidence the physician had regarding the appropriateness of his/her prescription on a scale from 0 to 10. A total of 30 clinical vignettes were created . AnswersThe primary outcome measure was the appropriate oral AT prescriptions defined as complying with guidelines in terms of the number of drugs, drug class, dosage and duration of prescription. The correct answers were based on the prescription support tool  and valiData from physicians’ answers were automatically integrated in a database for statistical analysis. The data were completely anonymous. In particular, neither the physician’s name nor email address was collected.The unit of measurement was the prescription . Considering that 85% of oral AT prescriptions would comply with guidelines in the control arm  and thatResults were expressed as the mean (standard deviation (SD)) or median ) for continuous variables and as numbers (percentages) for categorical variables. For the analysis of the primary outcome, we used an intent-to-treat analysis with a logistic mixed model with a clinical vignette effect and a physician effect nested in the trial arm taking into account that each participant intended to complete 3 clinical vignettes. Missing data were imputed by using multiple imputations with 20 imputed datasets  18]. Re. Re18]. www.cran.r-project.org).We performed sensitivity analyses for the handling of missing data with complete-case analysis  and modified intent-to-treat analysis . All analyses involved use of R v3.5.2  and 37 cardiologists (8%), between 5 November 2018 and 14 February 2019. In total, 238 were randomized to the experimental arm and 240 were randomized to the control arm .Baseline characteristics of randomized physicians are presented in n = 183) reported that at least 5% of their patients took an oral AT combination. Overall, 71% (n = 336) did not feel comfortable with these prescriptions  and 43% (n = 205) declared not knowing the guidelines for oral AT combinations or where to find them. Cardiologists felt more comfortable with these prescriptions  and more often knew where to find the guidelines (92% vs. 54%).Many physicians had to deal with prescriptions of oral AT combinations in their daily practice; indeed, 38%  of oral AT prescriptions were fully appropriate in the experimental arm versus 29.4% (n = 212) in the control arm: OR: 3.61 (95% CI 2.60 to 5.02)  . The mosto 5.02) . When a Physicians assigned to the experimental arm prescribed oral ATs more frequently in accordance with guidelines than did physicians assigned to the control arm when a single antiplatelet treatment was required , when a single anticoagulant treatment was required  and when a dual antiplatelet treatment was required  . There wWhen considering all clinical vignettes, each component of the prescription was significantly improved when physicians had access to the prescription support tool, with ORs ranging from 2 to 4 . Especiap < 0.001)  9 (IQR 6 to 9) vs. 6 (4 to 8)  . These d< 0.001) .n = 144) of physicians in the experimental arm evaluated the prescription support tool. They found it useful (median score (/10) 9 (IQR 8 to 10)), would be ready to use it (median score (/10) 9 (8 to 10)) and would recommend its use (median score (/10) 9 (8 to 10)) (n = 51) of physicians provided free-text comments, including the creation of a digital tool usable on a computer or smartphone for 12% of them ) . The sco of them .Sensitivity analyses performed regarding the handling of missing data gave results similar to the main analysis .p < 0.001). To our knowledge, this is the first study reporting such results.Among a sample of French physicians with clinical practice in outpatient settings, two-thirds were uncomfortable with prescribing oral AT combinations and almost half did not know where to find the recommendations. When evaluating clinical vignettes representing common clinical situations, only 29.4% of oral AT prescriptions were appropriate in the control arm , and the median self-reported degree of confidence these physicians had regarding the appropriateness of their prescriptions was 6 (/10) (IQR 4 to 8). The use of a dedicated prescription support tool synthesizing the guidelines on oral ATs led to significant improvement in the proportion of appropriate oral AT prescriptions ). Moreover, physicians felt much more confident prescribing according to the guidelines when they use the prescription support tool as compared to those who did not (median degree of confidence (/10): 9 (IQR 6 to 9), Overall, one-third of oral AT prescriptions were fully appropriate without access to the prescription support tool. This proportion is much lower than the 85% estimated rate from literature data  based onFrequent updating of recommendations  do not s2DS2VASc and HAS BLED algorithms [Our results also outline that many patients with atrial fibrillation who have an indication for chronic anticoagulant remain undertreated with an elevated risk of stroke ,21. The gorithms ,16,17. TThis prescription support tool is unique, including all national and international guidelines for the management of oral AT prescriptions in adult outpatients . To evalA large number of physicians who are used to prescribing oral ATs in their daily practice volunteered and were enrolled but a selection bias cannot be excluded. Conversely, non-access to the prescription support tool among the physicians assigned to the control arm could not be guaranteed, as was its use in the experimental arm. However, these potential biases would have reduced the impact of our tool.N = 19,798 outpatients) [Only a few cardiologists participated in the study despite multiple incentives and so reliable subgroup analyses by type of physicians could not be performed. Nevertheless, the target users of our tool are mainly general practitioners for several reasons. First, because comorbid conditions are very common in patients with cardiovascular disease , and patatients) , Barben More physicians in the experimental arm did not respond to their clinical vignettes than in the control arm. There was no impact of missing data, and sensitivity analyses gave similar results.Finally, even with access to the prescription support tool, only 55% of the prescriptions were fully appropriate, which could reflect the non-optimal format of the tool (median operation score (/10): 7 (IQR 5 to 9)) and/or the fact that physicians did not make complete use of it because there was no real clinical issue or because they thought they knew the answer. In fact, we do not know how many clinical vignettes have been completed using the tool. Fifty-one physicians in the experimental arm provided free-text comments about the tool. Twenty-four physicians found that the tool was difficult to read due to too small writing and too many abbreviations. By improving the format of the tool, and in particular its readability and ergonomics, we can expect a greater use and a better rate of appropriate oral AT prescriptions.A paper format of the tool is not suitable for frequent updating of guidelines on ATs, which occurs approximately every 5 years . This deOral AT prescriptions were three times more frequently appropriate when physicians had access to a prescription support tool than without. It should therefore interest all physicians caring for adults with neuro-cardiovascular pathologies requiring oral ATs  in order to prescribe with greater safety and confidence.