Abatacept in individuals at high risk of rheumatoid arthritis (APIPPRA): a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial.

BACKGROUND: Individuals with serum antibodies to citrullinated protein antigens (ACPA), rheumatoid factor, and symptoms, such as inflammatory joint pain, are at high risk of developing rheumatoid arthritis. In the arthritis prevention in the pre-clinical phase of rheumatoid arthritis with abatacept (APIPPRA) trial, we aimed to evaluate the feasibility, efficacy, and acceptability of treating high risk individuals with the T-cell co-stimulation modulator abatacept. METHODS: The APIPPRA study was a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial done in 28 hospital-based early arthritis clinics in the UK and three in the Netherlands. Participants (aged ≥18 years) at risk of rheumatoid arthritis positive for ACPA and rheumatoid factor with inflammatory joint pain were recruited. Exclusion criteria included previous episodes of clinical synovitis and previous use of corticosteroids or disease-modifying antirheumatic drugs. Participants were randomly assigned (1:1) using a computer-generated permuted block randomisation (block sizes of 2 and 4) stratified by sex, smoking, and country, to 125 mg abatacept subcutaneous injections weekly or placebo for 12 months, and then followed up for 12 months. Masking was achieved by providing four kits (identical in appearance and packaging) with pre-filled syringes with coded labels of abatacept or placebo every 3 months. The primary endpoint was the time to development of clinical synovitis in three or more joints or rheumatoid arthritis according to American College of Rheumatology and European Alliance of Associations for Rheumatology 2010 criteria, whichever was met first. Synovitis was confirmed by ultrasonography. Follow-up was completed on Jan 13, 2021. All participants meeting the intention-to-treat principle were included in the analysis. This trial was registered with EudraCT (2013-003413-18). FINDINGS: Between Dec 22, 2014, and Jan 14, 2019, 280 individuals were evaluated for eligibility and, of 213 participants, 110 were randomly assigned to abatacept and 103 to placebo. During the treatment period, seven (6%) of 110 participants in the abatacept group and 30 (29%) of 103 participants in the placebo group met the primary endpoint. At 24 months, 27 (25%) of 110 participants in the abatacept group had progressed to rheumatoid arthritis, compared with 38 (37%) of 103 in the placebo group. The estimated proportion of participants remaining arthritis-free at 12 months was 92·8% (SE 2·6) in the abatacept group and 69·2% (4·7) in the placebo group. Kaplan-Meier arthritis-free survival plots over 24 months favoured abatacept (log-rank test p=0·044). The difference in restricted mean survival time between groups was 53 days (95% CI 28-78; p<0·0001) at 12 months and 99 days (95% CI 38-161; p=0·0016) at 24 months in favour of abatacept. During treatment, abatacept was associated with improvements in pain scores, functional wellbeing, and quality-of-life measurements, as well as low scores of subclinical synovitis by ultrasonography, compared with placebo. However, the effects were not sustained at 24 months. Seven serious adverse events occurred in the abatacept group and 11 in the placebo group, including one death in each group deemed unrelated to treatment. INTERPRETATION: Therapeutic intervention during the at-risk phase of rheumatoid arthritis is feasible, with acceptable safety profiles. T-cell co-stimulation modulation with abatacept for 12 months reduces progression to rheumatoid arthritis, with evidence of sustained efficacy beyond the treatment period, and with no new safety signals. FUNDING: Bristol Myers Squibb.

Proving the Effectiveness of the Fundamentals of Robotic Surgery (FRS) Skills Curriculum: A Single-blinded, Multispecialty, Multi-institutional Randomized Control Trial.

OBJECTIVE: To demonstrate the noninferiority of the fundamentals of robotic surgery (FRS) skills curriculum over current training paradigms and identify an ideal training platform. SUMMARY BACKGROUND DATA: There is currently no validated, uniformly accepted curriculum for training in robotic surgery skills. METHODS: Single-blinded parallel-group randomized trial at 12 international American College of Surgeons (ACS) Accredited Education Institutes (AEI). Thirty-three robotic surgery experts and 123 inexperienced surgical trainees were enrolled between April 2015 and November 2016. Benchmarks (proficiency levels) on the 7 FRS Dome tasks were established based on expert performance. Participants were then randomly assigned to 4 training groups: Dome (n = 29), dV-Trainer (n = 30), and DVSS (n = 32) that trained to benchmarks and control (n = 32) that trained using locally available robotic skills curricula. The primary outcome was participant performance after training based on task errors and duration on 5 basic robotic tasks (knot tying, continuous suturing, cutting, dissection, and vessel coagulation) using an avian tissue model (transfer-test). Secondary outcomes included cognitive test scores, GEARS ratings, and robot familiarity checklist scores. RESULTS: All groups demonstrated significant performance improvement after skills training (P < 0.01). Participating residents and fellows performed tasks faster (DOME and DVSS groups) and with fewer errors than controls (DOME group; P < 0.01). Inter-rater reliability was high for the checklist scores (0.82-0.97) but moderate for GEARS ratings (0.40-0.67). CONCLUSIONS: We provide evidence of effectiveness for the FRS curriculum by demonstrating better performance of those trained following FRS compared with controls on a transfer test. We therefore argue for its implementation across training programs before surgeons apply these skills clinically.

Trainee Performance After Laparoscopic Simulator Training Using a Blackbox versus LapMentor.

BACKGROUND: Training using laparoscopic high-fidelity simulators (LHFSs) to proficiency levels improves laparoscopic cholecystectomy skills. However, high-cost simulators and their limited availability could negatively impact residents' laparoscopic training opportunities. We aimed to assess whether motivation and surgical skill performance differ after basic skills training (BST) using a low-cost (Blackbox) versus LHFS (LapMentor) among medical students. MATERIALS AND METHODS: Sixty-three medical students from Karolinska Institutet volunteered, completing written informed consent, questionnaire regarding expectations of the simulation training, and a visuospatial ability test. They were randomized into two groups that received BST using Blackbox (n = 32) or LapMentor (n = 31). However, seven students absence resulted in 56 participants, followed by another 9 dropouts. Subsequently, after training, 47 students took up three consecutive tests using the minimally invasive surgical trainer-virtual reality (MIST-VR) simulator, finalizing a questionnaire. RESULTS: More Blackbox group participants completed all MIST-VR tests (29/31 versus 18/25). Students anticipated mastering LapMentor would be more difficult than Blackbox (P = 0.04). In those completing the simulation training, a trend toward an increase was noted in how well participants in the Blackbox group liked the simulator training (P = 0.07). Subgroup analysis of motivation and difficulty in liking the training regardless of simulator was found only in women (Blackbox [P = 0.02]; LapMentor [P = 0.06]). In the Blackbox group, the perceived difficulty of training, facilitation, and liking the Blackbox training (significant only in women) were significantly correlated with the students' performance in the MIST-simulator. No such correlations were found in the LapMentor group. CONCLUSIONS: Results indicate an important role for low-tech/low-cost Blackbox laparoscopic BST of students in an otherwise high-tech surrounding. Furthermore, experience of Blackbox BST procedures correlate with students' performance in the MIST-VR simulator, with some gender-specific differences.

Validation of a Novel Needle Holder to Train Advanced Laparoscopy Skills to Novices in a Simulator Environment.

Background. Our aim was to determine if a newly designed Najar needle holder (NNH) shortens the time for novices to improve advanced laparoscopy (AL) techniques (suturing/knot tying), compared with a conventional macro needle holder (MNH) in a simulator. Furthermore, we aimed to validate a new video scoring system determining AL skills. Methods. Forty-six medical students performed identical surgical tasks in a prospective, crossover study evaluating AL skills (NNH vs MNH). All subjects performed a double-throw knot, 2 single-throw knots following 3 running sutures in the Simball Box (SB) simulator. After resting, subjects switched needle holders. All tasks were videotaped and analyzed using SB software and by 2 independent reviewers using the Objective Video Evaluation Scoring Table (OVEST). Trial performance expressed as SB Overall Score (SBOS) and OVEST. Results. In the group starting with NNH (followed by MNH) OVEST was consistently high during both trials (median = 12.5, range = 6.5-18.0, and median = 13.5, range = 6.5-21.0; P = .2360). However, in the group starting with MNH, OVEST improved significantly when the participants changed to NNH (median = 10.0, range = 2.5-19.5, vs median = 14.5, range = 4.5-18.0; P = .0003); an improvement was also found with SBOS (median = 37%, range = 27% to 92%, vs median = 48%, range = 34% to 70%; P = .0289). In both trials, both independent reviewers' OVEST measures correlated well: Trial 1: ß = 0.97, P < .0001; and Trial 2: ß = 0.95, P < .0001. A correlation also existed between SBOS and OVEST in both trials (ß = 2.1, P < .0001; and ß = 1.9, P = .0002). Conclusions. This study indicates a significantly higher improvement in laparoscopic suturing skills in novices training AL skills using NNH compared with MNH. Starting early, AL training in novices using NNH is a feasible option. Furthermore, OVEST used in experimental settings as an evaluation tool is comparable with the validated SBOS.

A longitudinal study of multiple lifestyle health risk behaviours among nursing students and non-nursing peers.

AIM: The aim of this paper is to compare the evolution of health risk behaviours between undergraduate nursing and social work students. BACKGROUND: Nursing includes the promotion of health and the shaping of healthy behaviours. An important determinant for providing lifestyle advice is the lifestyle of nurses themselves. DESIGN: Longitudinal comparative study. MEASUREMENTS: We compared lifestyle risk behaviours (binge drinking, cannabis/hashish/marijuana use, smoking, oral hygiene/toothbrushing, breakfast/fruit/vegetable consumption, physical activity and screen time/sedentary behaviours) using a self-administered standardized questionnaire in nursing (n = 121) and social work (n = 140) students at the beginning (2012) and the end of their studies (2015). Adjusted multivariable logistic/Poisson regression models were performed. RESULTS: There were no statistically significant differences between the departments in most risk factors in both assessments. However, in relation to their first year, both nursing and social work students displayed higher relative risk of engaging in more behavioural risk factors at the end of their studies (in delivery/junk food consumption, sunburns, hashish/marijuana use and multiple sexual partners). Social work students displayed better behaviours in physical activity and breakfast intake. CONCLUSION: Nursing students share the patterns of their nonnursing peers in behavioural risk factors compromising their future health and health-promoting role. We need strategies to safeguard the professional nursing practice.

Performance Assessment of Subjects With Nursing Education Trained in Sigmoidoscopy by Means of a Simulator.

Reports evaluating simulation-based sigmoidoscopy training among nurses are scarce. The aim of this prospective nonrandomized study was to assess the performance of nurses in simulated sigmoidoscopy training and the potential impact on their performance of endoscopy unit experience, general professional experience, and skills in manual activities requiring coordinated maneuvers. Forty-four subjects were included: 12 nurses with (Group A) and 14 nurses without endoscopy unit experience (Group B) as well as 18 senior nursing students (Group C). All received simulator training in sigmoidoscopy. Participants were evaluated with respect to predetermined validated metrics. Skills in manual activities requiring coordinated maneuvers were analyzed to draw possible correlations with their performance. The total population required a median number of 5 attempts to achieve all predetermined goals. Groups A and C outperformed Group B regarding the number of attempts needed to achieve the predetermined percentage of visualized mucosa (p = .017, p = .027, respectively). Furthermore, Group A outperformed Group B regarding the predetermined duration of procedure (p = .046). A tendency was observed for fewer attempts needed to achieve the overall successful endoscopy in both Groups A and C compared with Group B. Increased score on playing stringed instruments was associated with decreased total time of procedure (rs = -.34, p = .03) and with decreased number of total attempts for successful endoscopy (rs = -.31, p = .046). This study suggests that training nurses and nursing students in simulated sigmoidoscopy is feasible by means of a proper training program. Experience in endoscopy unit and skills in manual activities have a positive impact on the training process.

Video analysis in basic skills training: a way to expand the value and use of BlackBox training?

BACKGROUND: Basic skills training in laparoscopic high-fidelity simulators (LHFS) improves laparoscopic skills. However, since LHFS are expensive, their availability is limited. The aim of this study was to assess whether automated video analysis of low-cost BlackBox laparoscopic training could provide an alternative to LHFS in basic skills training. METHODS: Medical students volunteered to participate during their surgical semester at the Karolinska University Hospital. After written informed consent, they performed two laparoscopic tasks (PEG-transfer and precision-cutting) on a BlackBox trainer. All tasks were videotaped and sent to MPLSC for automated video analysis, generating two parameters (Pl and Prtcl_tot) that assess the total motion activity. The students then carried out final tests on the MIST-VR simulator. This study was a European collaboration among two simulation centers, located in Sweden and Greece, within the framework of ACS-AEI. RESULTS: 31 students (19 females and 12 males), mean age of 26.2 ± 0.8 years, participated in the study. However, since two of the students completed only one of the three MIST-VR tasks, they were excluded. The three MIST-VR scores showed significant positive correlations to both the Pl variable in the automated video analysis of the PEG-transfer (RSquare 0.48, P < 0.0001; 0.34, P = 0.0009; 0.45, P < 0.0001, respectively) as well as to the Prtcl_tot variable in that same exercise (RSquare 0.42, P = 0.0002; 0.29, P = 0.0024; 0.45, P < 0.0001). However, the correlations were exclusively shown in the group with less PC gaming experience as well as in the female group. CONCLUSIONS: Automated video analysis provides accurate results in line with those of the validated MIST-VR. We believe that a more frequent use of automated video analysis could provide an extended value to cost-efficient laparoscopic BlackBox training. However, since there are gender-specific as well as PC gaming experience differences, this should be taken in account regarding the value of automated video analysis.

Fast myocardial perfusion imaging with 99mTc in challenging patients using conventional SPECT cameras.

BACKGROUND: We attempted to validate the performance of a fast myocardial perfusion imaging (MPI) protocol in diagnostically challenging patients. METHODS: 78 patients with ΒΜΙ > 24.9, LVH or three vessels disease underwent two sequential gated-MPI studies. The first at 15 (Early Imaging, EI) and the second at 45 (Late Imaging, LI) minutes post 99mTc-injection, at both stress and rest. Counts over heart (H), liver (Liv) and subdiaphragmatic space (Sub) and image quality, and myocardial perfusion and function parameters were compared between the two protocols. Coronary angiography was performed within 2 months from MPI, and ROC analysis was used to compare the diagnostic accuracy for the detection of ≥50% diameter luminal stenosis. RESULTS: Quality was optimal-good in 93% of EI and 98% of LI studies (P = .12), H/Liv and stress H/Sub ratios were similar, but rest H/Sub ratio was lower in EI (P = .009). SSS [10 (0 to 46) vs 9 (0 to 36), P = .006] and SDS [3 (0 to 35) vs 2 (0 to 34), P = .02] were higher in EI protocol. LVEF, motion and thickening scores did not differ between the two protocols. A highly significant (P < .001) linear relationship with clinically negligible mean differences in Bland-Altman analysis was observed for all perfusion and function-related data. Sensitivity (EI 81%, LI 80%) and specificity (65% for both) did not differ (P = .23) between the two protocols. CONCLUSION: The fast protocol is technically feasible and diagnostically accurate compared to the established protocol in diagnostically challenging patients.

Striving for Better Medical Education: the Simulation Approach.

Medical simulation is a rapidly expanding area within medical education due to advances in technology, significant reduction in training hours and increased procedural complexity. Simulation training aims to enhance patient safety through improved technical competency and eliminating human factors in a risk free environment. It is particularly applicable to a practical, procedure-orientated specialties. Simulation can be useful for novice trainees, experienced clinicians (e.g. for revalidation) and team building. It has become a cornerstone in the delivery of medical education, being a paradigm shift in how doctors are educated and trained. Simulation must take a proactive position in the development of metric-based simulation curriculum, adoption of proficiency benchmarking definitions, and should not depend on the simulation platforms used. Conversely, ingraining of poor practice may occur in the absence of adequate supervision, and equipment malfunction during the simulation can break the immersion and disrupt any learning that has occurred. Despite the presence of high technology, there is a substantial learning curve for both learners and facilitators. The technology of simulation continues to advance, offering devices capable of improved fidelity in virtual reality simulation, more sophisticated procedural practice and advanced patient simulators. Simulation-based training has also brought about paradigm shifts in the medical and surgical education arenas and ensured that the scope and impact of simulation will continue to broaden.

A simple sensor calibration technique for estimating the 3D pose of endoscopic instruments.

INTRODUCTION: The aim of this study was to describe a simple and easy-to-use calibration method that is able to estimate the pose (tip position and orientation) of a rigid endoscopic instrument with respect to an electromagnetic tracking device attached to the handle. METHODS: A two-step calibration protocol was developed. First, the orientation of the instrument shaft is derived by performing a 360° rotation of the instrument around its shaft using a firmly positioned surgical trocar. Second, the 3D position of the instrument tip is obtained by allowing the tip to come in contact with a planar surface. RESULTS: The results indicate submillimeter accuracy in the estimation of the tooltip position, and subdegree accuracy in the estimation of the shaft orientation, both with respect to a known reference frame. The assets of the proposed method are also highlighted by illustrating an indicative application in the field of augmented reality simulation. CONCLUSIONS: The proposed method is simple, inexpensive, does not require employment of special calibration frames, and has potential applications not only in training systems but also in the operating room.

A novel augmented reality simulator for skills assessment in minimal invasive surgery.

INTRODUCTION: Over the past decade, simulation-based training has come to the foreground as an efficient method for training and assessment of surgical skills in minimal invasive surgery. Box-trainers and virtual reality (VR) simulators have been introduced in the teaching curricula and have substituted to some extent the traditional model of training based on animals or cadavers. Augmented reality (AR) is a new technology that allows blending of VR elements and real objects within a real-world scene. In this paper, we present a novel AR simulator for assessment of basic laparoscopic skills. METHODS: The components of the proposed system include: a box-trainer, a camera and a set of laparoscopic tools equipped with custom-made sensors that allow interaction with VR training elements. Three AR tasks were developed, focusing on basic skills such as perception of depth of field, hand-eye coordination and bimanual operation. The construct validity of the system was evaluated via a comparison between two experience groups: novices with no experience in laparoscopic surgery and experienced surgeons. The observed metrics included task execution time, tool pathlength and two task-specific errors. The study also included a feedback questionnaire requiring participants to evaluate the face-validity of the system. RESULTS: Between-group comparison demonstrated highly significant differences (<0.01) in all performance metrics and tasks denoting the simulator's construct validity. Qualitative analysis on the instruments' trajectories highlighted differences between novices and experts regarding smoothness and economy of motion. Subjects' ratings on the feedback questionnaire highlighted the face-validity of the training system. CONCLUSIONS: The results highlight the potential of the proposed simulator to discriminate groups with different expertise providing a proof of concept for the potential use of AR as a core technology for laparoscopic simulation training.

A Web simulation of medical image reconstruction and processing as an educational tool.

Web educational resources integrating interactive simulation tools provide students with an in-depth understanding of the medical imaging process. The aim of this work was the development of a purely Web-based, open access, interactive application, as an ancillary learning tool in graduate and postgraduate medical imaging education, including a systematic evaluation of learning effectiveness. The pedagogic content of the educational Web portal was designed to cover the basic concepts of medical imaging reconstruction and processing, through the use of active learning and motivation, including learning simulations that closely resemble actual tomographic imaging systems. The user can implement image reconstruction and processing algorithms under a single user interface and manipulate various factors to understand the impact on image appearance. A questionnaire for pre- and post-training self-assessment was developed and integrated in the online application. The developed Web-based educational application introduces the trainee in the basic concepts of imaging through textual and graphical information and proceeds with a learning-by-doing approach. Trainees are encouraged to participate in a pre- and post-training questionnaire to assess their knowledge gain. An initial feedback from a group of graduate medical students showed that the developed course was considered as effective and well structured. An e-learning application on medical imaging integrating interactive simulation tools was developed and assessed in our institution.

The Effect of Mixed-Task Basic Training in the Acquisition of Advanced Laparoscopic Skills.

The aim of this study was to assess whether mixed practice of basic tasks on a virtual reality (VR) simulator improves the performance of advanced tasks on the same device used for training as well as on a video trainer (VT). Thirty-six novices were allocated into 3 equal groups. Each group practiced on different combinations of basic tasks on a VR simulator: (A) peg transfer, (B) peg transfer and clipping, and (C) peg transfer, clipping, and cutting. Before and after training, each group performed a laparoscopic cholecystectomy (LC) scenario on the simulator and intracorporeal knot tying (KT) on a VT. Assessment metrics included time, instrument's path length, penalty score, and hand motion synchronization. Results showed that for the common training tasks, plateau values were statistically equivalent for most assessment metrics (P > .05). For LC, all groups showed significant performance improvement (P < .05). For KT, group C improved significantly in pathlength (P < .005), penalty score (P < .05), and hand motion synchronization (P < .05); the other groups failed to show an improvement (P > .05). In conclusion, training on different VR tasks seems to have no effect on the performance of more demanding tasks on the same device. However, the number of different tasks practiced on the VR simulator seems to favorably affect the performance of advanced tasks on the VT.

Comparison of the Sensor-Augmented Pump System with the Advanced Hybrid Closed-Loop Delivery System: Quality of Life, Diabetes Distress, and Glycaemic Outcomes in a Real-Life Context.

BACKGROUND: Type 1 diabetes mellitus (T1D) is a chronic disease that requires exogenous insulin administration and intensive management to prevent any complications. Recent innovations in T1D management technologies include the Advanced Hybrid Closed-Loop delivery system (AHCL). The pioneer AHCL system provides automated basal and automated bolus corrections when needed. OBJECTIVE: This study aimed to compare the Advanced Hybrid Closed-Loop (AHCL) system and the Sensor-Augmented Pump (SAP) with Predictive Low Glucose Management (PLGM) system, in relation to glycaemic outcomes, general and diabetes-related Quality of Life (QoL), and diabetes distress. METHODS: General and diabetes-related QoL were assessed with the Diabetes Quality of Life Brief Clinical Inventory (DQOL-BCI) and the World Health Organization Quality of Life-BREF (WHOQOL-BREF), respectively. Diabetes distress was assessed with the Diabetes Distress Scale for Type 1 diabetes (T1-DDS). RESULTS: Eighty-nine T1D adults participated in the study, mostly females (65.2%), with a mean age of 39.8 (± 11.5 years). They had on average 23 years of diabetes (± 10.7) and they were on continuous subcutaneous insulin infusion therapy. Significant differences favoring the AHCL over the SAP + PLGM system were demonstrated by lower mean glucose levels, less time above range, lower scores on DQOL-BCI, T1-DDS, and higher scores on WHOQOL-BREF. Finally, the linear regression models revealed the association of time in range in most of the above aspects. CONCLUSION: This study highlighted the advantages of the AHCL system over the SAP + PLGM system in the real-world setting in relation to general and diabetes-related QoL, diabetes distress, and glycaemic outcomes.

Glued suture-less peritoneum closure in laparoscopic inguinal hernia repair reduces acute postoperative pain.

Inguinal hernia repair is performed more than 20 million times per annum, representing a significant health and economic burden. Over the last three decades, significant technical advances have started to reduce the invasiveness of these surgeries, which translated to better recovery and reduced costs. Here we bring forward an innovative surgical technique using a biodegradable cyanoacrylate glue instead of a traumatic suture to close the peritoneum, which is a highly innervated tissue layer, at the end of endoscopy hernia surgery. To test how this affects the invasiveness of hernia surgery, we conducted a cohort study. A total of 183 patients that underwent minimally invasive hernia repair, and the peritoneum was closed with either a conventional traumatic suture (n = 126, 68.9%) or our innovative approach using glue (n = 57, 31.1%). The proportion of patients experiencing acute pain after surgery was significantly reduced (36.8 vs. 54.0%, p = 0.032) by using glue instead of a suture. In accordance, the mean pain level was higher in the suture group (VAS = 1.5 vs. 1.3, p = 0.029) and more patients were still using painkillers (77.9 vs. 52.4%, p = 0.023). Furthermore, the rate of complications was not increased in the glue group. Using multivariate regressions, we identified that using a traumatic suture was an independent predictor of acute postoperative pain (OR 2.0, 95% CI 1.1-3.9, p = 0.042). In conclusion, suture-less glue closure of the peritoneum is innovative, safe, less painful, and possibly leads to enhanced recovery and decreased health costs.

Metabolic syndrome in adolescence: can it be predicted from natal and parental profile? The Prediction of Metabolic Syndrome in Adolescence (PREMA) study.

BACKGROUND: There are well-established predisposing factors for the development of metabolic syndrome (MetS) in childhood or adolescence, but no specific risk profile has been identified as yet. The Prediction of Metabolic Syndrome in Adolescence (PREMA) study was conducted (1) to construct a classification score that could detect children at high risk for MetS in adolescence and (2) to test its predictive accuracy. METHODS AND RESULTS: In the derivation cohort (1270 children), data from natal and parental profile and from initial laboratory assessment at 6 to 8 years of age were used to detect independent predictors of MetS at 13 to 15 years of age according to the International Diabetes Federation definition. In the validation cohort (1091 adolescents), the discriminatory capacity of the derived prediction score was tested on an independent adolescent population. MetS was diagnosed in 105 adolescents in the derivation phase (8%), whereas birth weight <10th percentile (odds ratio, 6.02; 95% confidence interval, 2.53-10.12, P<0.001), birth head circumference <10th percentile (odds ratio, 4.15; 95% confidence interval, 2.04-7.14, P<0.001), and parental overweight or obesity (in at least 1 parent; odds ratio, 3.22; 95% confidence interval, 1.30-5.29, P<0.01) were independently associated with diagnosis of MetS in adolescence. Among adolescents in the validation cohort (86 [8%] with MetS), the presence of all these 3 predictors predicted MetS with a sensitivity of 91% and a specificity of 98%. CONCLUSIONS: The coexistence of low birth weight, small head circumference, and parental history of overweight or obesity may be useful for detection of children at risk of developing MetS in adolescence.

Diabetes Mellitus Type 1 During COVID-19: Psychological Symptoms and Eating Attitudes.

BACKGROUND: Diabetes Mellitus Type 1 is a chronic metabolic disorder, the treatment of which extremely burdens the patient. The lockdown, as a measure to prevent the spreading of the 2019 coronavirus disease, was a major challenge for the general public. People with chronic diseases, such as T1D patients, have complex emotional and psychological needs and are at increased risk for both depressive symptoms and anxiety. OBJECTIVE: The aim of this study was to evaluate the impact of body mass index of T1D patients on the psychological symptoms and eating habits, as well as the prognostic factors of the psychological symptoms during the lockdown period. METHODS: Diabetes mellitus patients were invited to complete this survey from the outpatient Diabetes clinic of the General Hospital of Chania and the "AHEPA" General University Hospital of Thessaloniki in Greece. Psychological symptoms were assessed using the DASS-42 questionnaire, and eating habits were assessed using the EAT-26 questionnaire. RESULTS: Overall, 112 T1D patients were analyzed (response rate: 28.8%). Obese T1D patients appear to be at greater risk of developing psychological symptoms, such as depression, anxiety, and stress. Furthermore, disordered eating behaviors and bulimia and food preoccupation subscale are associated with psychological symptoms. CONCLUSION: The findings suggest that obese T1D patients are at greater risk of developing psychological symptoms. Moreover, when an eating disorder is triggered, negative psychological symptoms such as depression and anxiety are reduced. The results of this study may guide targeted interventions among T1D patients.

Optimized immunosuppression to prevent graft failure in renal transplant recipients with HLA antibodies (OuTSMART): a randomised controlled trial.

Background: 3% of kidney transplant recipients return to dialysis annually upon allograft failure. Development of antibodies (Ab) against human leukocyte antigens (HLA) is a validated prognostic biomarker of allograft failure. We tested whether screening for HLA Ab, combined with an intervention to improve adherence and optimization of immunosuppression could prevent allograft failure. Methods: Prospective, open-labelled randomised biomarker-based strategy (hybrid) trial in 13 UK transplant centres [EudraCT (2012-004308-36) and ISRCTN (46157828)]. Patients were randomly allocated (1:1) to unblinded or double-blinded arms and screened every 8 months. Unblinded HLA Ab+ patients were interviewed to encourage medication adherence and had tailored optimisation of Tacrolimus, Mycophenolate mofetil and Prednisolone. The primary outcome was time to graft failure in an intention to treat analysis. The trial had 80% power to detect a hazard ratio of 0.49 in donor specific antibody (DSA)+ patients. Findings: From 11/9/13 to 27/10/16, 5519 were screened for eligibility and 2037 randomised (1028 to unblinded care and 1009 to double blinded care). We identified 198 with DSA and 818 with non-DSA. Development of DSA, but not non-DSA was predictive of graft failure. HRs for graft failure in unblinded DSA+ and non-DSA+ groups were 1.54 (95% CI: 0.72 to 3.30) and 0.97 (0.54-1.74) respectively, providing no evidence of an intervention effect. Non-inferiority for the overall unblinded versus blinded comparison was not demonstrated as the upper confidence limit of the HR for graft failure exceeded 1.4 (1.02, 95% CI: 0.72 to 1.44). The only secondary endpoint reduced in the unblinded arm was biopsy-proven rejection. Interpretation: Intervention to improve adherence and optimize immunosuppression does not delay failure of renal transplants after development of DSA. Whilst DSA predicts increased risk of allograft failure, novel interventions are needed before screening can be used to direct therapy. Funding: The National Institute for Health Research Efficacy and Mechanism Evaluation programme grant (ref 11/100/34).

A head-to-head comparison between virtual reality and physical reality simulation training for basic skills acquisition.

BACKGROUND: This study aimed to investigate whether basic laparoscopic skills acquired with a virtual reality simulator (LapVR™) are transferable to a standard video trainer (VT) and vice versa. METHODS: Three basic tasks were considered: peg transfer, cutting, and knot-tying. The physical models were custom-built as identical copies of the virtual models. Forty-four novices were randomized into two equal groups to be trained on the LapVR™ or the VT. Each task was practiced separately 12 times. Transferability of skills from one modality to the other was assessed by performing the same task on the alternative modality before and after training (crossover assessment). Performance metrics included path length, time, and penalty score. RESULTS: Both groups demonstrated significant performance curves for all tasks and metrics (p < 0.05). Plateaus were statistically equivalent between the groups for each task in terms of path length and time, and across all tasks in terms of the penalty score (p < 0.05). When each group was tested on the alternative modality there was a significant improvement for all tasks and metrics (p < 0.05). Comparing the plateau performance of one group with the performance achieved on the same simulator by the other group we found (a) no statistical deference in the penalty score (p < 0.05), (b) a statistical difference in time and path length for cutting and knot-tying (p < 0.05), and (c) an equal time performance for peg transfer (p < 0.05) but not for path length (p < 0.05). CONCLUSIONS: Both modalities provided significant enhancement of the novices' performance. The skills learned on the LapVR™ are transferable to the VT and vice versa. However, training with one modality does not necessarily mean a performance equivalent to that achieved with the other modality.