Do prerecorded lecture VODcasts affect lecture attendance of first-yearpre-clinical Graduate Entry to Medicine students?

Background: There is increasing concern amongst educators that the provision of recorded lectures may reduce student attendance of live lectures. We therefore sought to determine if the provision of prerecorded lecture video podcasts (VODcasts) to first-year Graduate Entry to Medicine (GEM) students, affected attendance at 21 Physiology lectures within three separate pre-clinical modules.

Methods: Data on lecture attendance, utilization of VODcasts, and whether VODcasts should replace live lectures were drawn from three surveys conducted in academic years 2014–2015 and 2015–2016 on all first-year GEM students in two first-year pre-clinical modules where prerecorded Physiology VODcasts were available for viewing or downloading prior to scheduled live lectures.

Results: A total of 191/214 (89%) students responded to the three surveys, with 84.3% of students attending all 21 lectures in the study. Only 4% of students missed more than one lecture in each of the three lecture series, with 79% indicating that VODcasts should not replace lectures.

Conclusion: Therefore, we conclude that the attendance of pre-clinical GEM students at live lectures is not significantly impacted upon by the provision of lecture VODcasts, with most students viewing them as useful revision tools rather than as a replacement for live lectures.     

Platelet Function and Genotype after DES Implantation in East Asian Patients: Rationale and Characteristics of the PTRG-DES Consortium

PurposePlatelet function test (PFT) results and genotype hold unique prognostic implications in East Asian patients. The aim of the PTRG-DES (Platelet function and genoType-Related long-term proGnosis in Drug-Eluting Stent-treated Patients with coronary artery disease) consortium is to assess the clinical impact thereof on long-term clinical outcomes in Korean patients with coronary artery disease during dual antiplatelet therapy (DAPT) including clopidogrel.Materials and MethodsSearching publications on the PubMed, we reviewed clopidogrel treatment studies with PFT and/or genotype data for potential inclusion in this study. Lead investigators were invited to share PFT/genotype results, patient characteristics, and clinical outcomes to evaluate relationships among them.ResultsNine registries from 32 academic centers participated in the PTRG-DES consortium, contributing individual patient data from 13160 patients who underwent DES implantation between July 2003 and August 2018. The PTRG-PFT cohort was composed of 11714 patients with available VerifyNow assay results. Platelet reactivity levels reached 218±79 P2Y12 reaction units (PRU), and high on-clopidogrel platelet reactivity based on a consensus-recommended cutoff (PRU >208) was observed in 55.9%. The PTRG-Genotype cohort consisted of 8163 patients with candidate genotypes related with clopidogrel responsiveness. Of those with cytochrome P450 (CYP) 2C19 genotype, frequencies of carrying one and two loss-of-function allele (s) (^*2 or ^*3) were 47.9% (intermediate metabolizers) and 14.2% (poor metabolizers), respectively.ConclusionThe PTRG-DES consortium highlights unique values for on-clopidogrel platelet reactivity and CYP2C19 phenotype that may be important to developing optimal antiplatelet regimens in East Asian patients.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT04734028","term_id":"NCT04734028"}}NCT04734028.     

UGT1A1 promoter polymorphism increases risk of nilotinib-induced hyperbilirubinemia.

Nilotinib is a novel BCR-ABL inhibitor with significantly improved potency and selectivity over imatinib. In Phase I and Phase II clinical studies of nilotinib in patients with a variety of leukemias, infrequent instances of reversible, benign elevation of bilirubin were observed. Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) glucuronidates bilirubin in humans, and a polymorphism in the promoter of the gene that encodes it has been associated with hyperbilirubinemia during treatment with a number of drugs. Pharmacogenetic analysis of that TA-repeat polymorphism found an association between the (TA)7/(TA)7 genotype and risk of hyperbilirubinemia in Phase I patients with imatinib-resistant/intolerant chronic myeloid leukemia (CML) or relapsed/refractory Ph+ acute lymphoblastic leukemia (ALL); this result was replicated in two separate analyses of the chronic phase (CP) and accelerated phase (AP) CML arms of a Phase II study. As nilotinib is not known to be glucuronidated by UGT1A1, the combined impact of inhibition of UGT1A1 activity by nilotinib and genetic polymorphism is the most likely cause of the increased rate of hyperbilirubinemia.     

Novel sigma (sigma) receptor agonists produce antidepressant-like effects in mice.

Many antidepressant drugs interact with sigma receptors and accumulating evidence suggests that these proteins mediate antidepressant-like effects in animals and humans. sigma Receptors are localized in brain regions affected in depression, further strengthening the hypothesis that they represent logical drug development targets. In this study, two novel sigma receptor agonists (UMB23, UMB82) were evaluated for antidepressant-like activity in mice. First, radioligand binding studies confirmed that the novel compounds had preferential affinity for sigma receptors. Second, the forced swim test, a well established animal model for screening potential antidepressant drugs, showed that both compounds dose-dependently reduced immobility time. The sigma receptor antagonist BD1047 attenuated the antidepressant-like effects of UMB23 and UMB82. Third, locomotor activity suggested that the effects of UMB23 and UMB82 in the forced swim test were not due to non-specific motor activating effects. Together, the data provide further evidence that sigma receptor agonists represent a possible new class of antidepressant medication.     

Risperidone and 9-hydroxyrisperidone concentrations are not dependent on age or creatinine clearance among elderly subjects

Risperidone is extensively metabolized to an active metabolite, 9-hydroxyrisperidone (9-OH), which is dependent on renal clearance. Risperidone and 9-OH clearances are reduced in the elderly when compared to young subjects. The objective of this study was to determine whether among elderly subjects, risperidone and 9-OH clearance would further decline with increasing age and decreasing creatinine clearance (CrCl). Twenty geriatric inpatients were evaluated in a naturalistic setting with regard to total daily risperidone dose and dosing interval. Creatinine clearance was determined using an 8-hour urine collection. Risperidone and 9-OH concentrations were determined by radioimmunoassay. Spearman's correlation coefficients were used to examine the impact of age and CrCl on concentrations of risperidone, 9-OH, their sum, and the quotient of 9-OH/risperidone. Mean age was 76.4 +/- 9 years (range 56-91). Mean CrCl was 55.4 +/- 32.8 mL/min/1.73 m2 (range 17-142 mL/min/1.73 m2). Mean risperidone daily dose was 1.3 +/- 0.7 mg. Steady-state risperidone and 9-OH concentrations were 4.1 +/- 5.3 ng/mL and 9.1 +/- 6.2 ng/mL, respectively. Mean 9-OH/risperidone was 6.2 +/- 6.1. Concentrations of risperidone, 9-OH, their sum, and 9-OH/risperidone were not significantly correlated with age or CrCl. These results were unchanged when concentrations were corrected for total daily risperidone dose. Among elderly subjects, risperidone and 9-OH clearance do not decline with increasing age or declining CrCl.     

The ictal EEG as a predictive factor for outcome following corpus callosum section in adults

Published reports have indicated that after callosotomy half or more of all patients will experience a 50% or greater reduction in seizure frequency. Those callosotomy patients whose seizures produce falls appear to have the best results. We studied the value of ictal EEG in 41 patients 18 years or older who had undergone either a total or partial callosotomy at our program. Ictal EEG's were separated into two categories: Type I: generalized slow spike wave, electrodecrement, non-evolving low amplitude fast activity; Type II: all other patterns. Types I and II were then compared to a defined one-year outcome for the targeted seizure type using Chi-square or Fishers Exact Test. Previously identified predictors of good or worthwhile outcome as defined by the literature were also evaluated. RESULTS: A significant association was noted for presence of specifically defined EEG patterns and a 90% reduction in seizure frequency but not for other factors analyzed. CONCLUSION: The ictal EEG but not other factors is able to identify a group of patients who have a better than 90% chance for total or nearly total resolution of seizures causing sudden falls.