National Implementation of Simulator Training Improves Transurethral Resection of Bladder Tumours in Patients

BACKGROUND: Transurethral resection of bladder tumours (TURBT) is the initial diagnostic treatment for patients with bladder cancer. TURBT is not an easy procedure to master and simulator training may play a role in improving the learning curve. OBJECTIVE: To implement a national training programme for simulation-based mastery learning in TURBT and explore operating theatre performance after training. DESIGN, SETTING, AND PARTICIPANTS: From June 2019 to March 2021, 31 doctors at urology departments in Denmark performed two pretraining TURBT procedures on patients, followed by proficiency-based mastery learning on a virtual reality simulator and then two post-training TURBTs on patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Operating theatre performances were video-recorded and assessed by two independent, blinded raters using the Objective Structured Assessment for Transurethral Resection of Bladder Tumours Skills (OSATURBS) assessment tool. Paired-sample t tests were used to compare pretraining and post-training analyses and independent t tests for between-group comparisons. This trial is registered at ClinicalTrials.gov as NCT03864302. RESULTS AND LIMITATIONS: Before training, novices had significantly lower performance scores in comparison to those with intermediate experience (p = 0.017) and experienced doctors (p < 0.001). After training, novices significantly improved their clinical performance score (from 11.4 to 17.1; p = 0.049, n = 10). Those with intermediate experience and experienced doctors did not benefit significantly from simulator training (p = 0.9 and p = 0.8, respectively). CONCLUSIONS: Novices improved their TURBT performance in the operating theatre after completing a proficiency-based training programme on a virtual reality simulator. PATIENT SUMMARY: We trained surgeons in an operation to remove bladder tumours using a virtual reality simulator. Novice doctors improved their performance significantly after the training, but the training effects for more experienced doctors were minimal. Therefore, we suggest the introduction of mandatory simulator training in the residency programme for urologists

Mutations in KCNT1 cause a spectrum of focal epilepsies

Summary Autosomal dominant mutations in the sodium-gated potassium channel subunit gene KCNT1 have been associated with two distinct seizure syndromes, nocturnal frontal lobe epilepsy (NFLE) and malignant migrating focal seizures of infancy (MMFSI). To further explore the phenotypic spectrum associated with KCNT1, we examined individuals affected with focal epilepsy or an epileptic encephalopathy for mutations in the gene. We identified KCNT1 mutations in 12 previously unreported patients with focal epilepsy, multifocal epilepsy, cardiac arrhythmia, and in a family with sudden unexpected death in epilepsy (SUDEP), in addition to patients with NFLE and MMFSI. In contrast to the 100% penetrance so far reported for KCNT1 mutations, we observed incomplete penetrance. It is notable that we report that the one KCNT1 mutation, p.Arg398Gln, can lead to either of the two distinct phenotypes, ADNFLE or MMFSI, even within the same family. This indicates that genotype-phenotype relationships for KCNT1 mutations are not straightforward. We demonstrate that KCNT1 mutations are highly pleiotropic and are associated with phenotypes other than ADNFLE and MMFSI. KCNT1 mutations are now associated with Ohtahara syndrome, MMFSI, and nocturnal focal epilepsy. They may also be associated with multifocal epilepsy and cardiac disturbances

Gene Panel Testing in Epileptic Encephalopathies and Familial Epilepsies

In recent years, several genes have been causally associated with epilepsy. However, making a genetic diagnosis in a patient can still be difficult, since extensive phenotypic and genetic heterogeneity has been observed in many monogenic epilepsies. This study aimed to analyze the genetic basis of a wide spectrum of epilepsies with age of onset spanning from the neonatal period to adulthood. A gene panel targeting 46 epilepsy genes was used on a cohort of 216 patients consecutively referred for panel testing. The patients had a range of different epilepsies from benign neonatal seizures to epileptic encephalopathies (EEs). Potentially causative variants were evaluated by literature and database searches, submitted to bioinformatic prediction algorithms, and validated by Sanger sequencing. If possible, parents were included for segregation analysis. We identified a presumed disease-causing variant in 49 (23%) of the 216 patients. The variants were found in 19 different genes including SCN1A, STXBP1, CDKL5, SCN2A, SCN8A, GABRA1, KCNA2, and STX1B. Patients with neonatal-onset epilepsies had the highest rate of positive findings (57%). The overall yield for patients with EEs was 32%, compared to 17% among patients with generalized epilepsies and 16% in patients with focal or multifocal epilepsies. By the use of a gene panel consisting of 46 epilepsy genes, we were able to find a disease-causing genetic variation in 23% of the analyzed patients. The highest yield was found among patients with neonatal-onset epilepsies and EEs