Mandrekar, Jayawant N.

Abstract OBJECTIVE Using individual pharmacogenomic phenotypes to investigate the factors affecting the efficacy and tolerability of verapamil for migraine prevention. BACKGROUND Verapamil has a wide range of dosing in headache disorders without reliable tools to predict the optimal doses for an individual. METHODS This is a retrospective chart review examining adults with existing pharmacogenomic reports at Mayo Clinic who had used verapamil for migraine. Effects of six cytochrome P450 phenotypes on the minimum effective and maximum tolerable verapamil doses for migraine prevention were assessed. RESULTS The mean minimum effective and maximum tolerable doses for the 33 patients in final analysis were 178.2(20–320) mg and 227.9(20–480) mg. A variety of CYP2C9, CYP2D6, and CYP3A5 phenotypes were found, without significant association with the verapamil doses after adjusting for age, sex, body mass index, and smoking status. CONCLUSIONS We demonstrated a wide range of effective and tolerable verapamil doses used for migraine in a cohort with various pharmacogenomic phenotypes.

The antibiofilm activity of a hypochlorous acid (HOCl)-producing electrochemical bandage (e-bandage) was assessed against 14 yeast isolates in vitro . The evaluated e-bandage was polarized at +1.5 V Ag/AgCl to allow continuous production of HOCl.

Abstract Background Increasing antimicrobial resistance combined with a lagging pipeline of novel antimicrobial compounds have resulted in a resurgence of interest in phage therapy. To select optimal phage or phage combinations for patients for whom phage therapy is considered, assessment of activity of a panel of phages against the patients’ bacterial isolate(s) should ideally be performed. Classical phage susceptibility testing methods (i.e., agar overlay) may be laborious, with expertise outside of normal training and competency of medical laboratory science staff needed. Content Adaptive Phage Therapeutics™ leveraged a commercially available phenotyping system (Biolog OmniLog®) to generate the PhageBank Susceptibility Test™, which uses a custom data analysis pipeline (PhageSelect™) to measure the delay in reaching log-phase metabolic activity (“hold time”) when a given isolate is challenged with a specific phage. The goal of this study was to preliminarily assess reproducibility of this approach by testing 2 bacterial species at 2 sites, APT and an academic site. Nineteen Escherichia coli phages were tested against 18 bacterial isolates, and 21 Staphylococcus aureus phages, against 11 bacterial isolates. Result comparisons were statistically excellent for E. coli (κ = 0.7990) and good/fair for S. aureus (κ = 0.6360). Summary The described method provides good/fair to excellent statistical reproducibility for assessment of phage susceptibility of 2 commonly encountered bacterial species.

Aims The aim of this study was to determine the diagnostic accuracy of α defensin (AD) lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) tests for periprosthetic joint infection (PJI) in comparison to conventional synovial white blood cell (WBC) count and polymorphonuclear neutrophil percentage (PMN%) analysis. Methods Patients undergoing joint aspiration for evaluation of pain after total knee arthroplasty (TKA) or total hip arthroplasty (THA) were considered for inclusion. Synovial fluids from 99 patients (25 THA and 74 TKA) were analyzed by WBC count and PMN% analysis, AD LFA, and AD ELISA. WBC and PMN% cutoffs of ≥ 1,700 cells/mm3 and ≥ 65% for TKA and ≥ 3,000 cells/mm3 and ≥ 80% for THA were used, respectively. A panel of three physicians, all with expertise in orthopaedic infections and who were blinded to the results of AD tests, independently reviewed patient data to diagnose subjects as with or without PJI. Consensus PJI classification was used as the reference standard to evaluate test performances. Results were compared using McNemar’s test and area under the receiver operating characteristic curve (AUC) analysis. Results Expert consensus classified 18 arthroplasies as having failed due to PJI and 81 due to aseptic failure. Using these classifications, the calculated sensitivity and specificity of AD LFA was 83.3% (95% confidence interval (CI) 58.6 to 96.4) and 93.8% (95% CI 86.2 to 98.0), respectively. Sensitivity and specificity of AD ELISA was 83.3% (95% CI 58.6 to 96.4) and 96.3% (95% CI 89.6 to 99.2), respectively. There was no statistically significant difference between sensitivity (p = 1.000) or specificity (p = 0.157) of the two AD assays. AUC for AD LFA was 0.891. In comparison, AUC for synovial WBC count, PMN%, and the combination of the two values was 0.821 (sensitivity p = 1.000, specificity p < 0.001), 0.886 (sensitivity p = 0.317, specificity p = 0.011), and 0.926 (sensitivity p = 0.317, specificity p = 0.317), respectively. Conclusion The diagnostic accuracy of synovial AD for PJI diagnosis is comparable and not statistically superior to that of synovial WBC count plus PMN% combined. Cite this article: Bone Joint J 2021;103-B(6):1119–1126.

Helicobacter pylori infection is mainly diagnosed noninvasively, with susceptibility testing traditionally requiring endoscopy. Treatment is empirical, with clarithromycin-based triple therapy recommended where resistance rates are below 15%. Rising rates of clarithromycin resistance, resulting in high therapy failure rates, are seen worldwide, but U.S. data are limited.

Background There has been limited research on the positive aspects of physician wellness and to our knowledge there have been no validity studies on measures of resilience and grit among internal medicine (IM) residents. Objectives To investigate the validity of resilience (10 items Connor-Davidson Resilience Scale (CD-RISC 10)) and grit (Short Grit Scale (GRIT-S)) scores among IM residents at a large academic centre, and assess potential associations with previously validated measures of medical knowledge, clinical performance and professionalism. Methods We evaluated CD-RISC 10 and GRIT-S instrument scores among IM residents at the Mayo Clinic Rochester, Minnesota between July 2017 and June 2019. We analysed dimensionality, internal consistency reliability and criterion validity in terms of relationships between resilience and grit, with standardised measures of residents’ medical knowledge (in-training examination (ITE)), clinical performance (faculty and peer evaluations and Mini-Clinical Evaluation Examination (mini-CEX)) and professionalism/dutifulness (conference attendance and evaluation completion). Results A total of 213 out of 253 (84.2%) survey-eligible IM residents provided both CD-RISC 10 and GRIT-S survey responses. Internal consistency reliability (Cronbach alpha) was excellent for CD-RISC 10 (0.93) and GRIT-S (0.82) overall, and for the GRIT subscales of consistency of interest (0.84) and perseverance of effort (0.71). CD-RISC 10 scores were negatively associated with ITE percentile (β=−3.4, 95% CI −6.2 to −0.5, p=0.02) and mini-CEX (β=−0.2, 95% CI −0.5 to −0.02, p=0.03). GRIT-S scores were positively associated with evaluation completion percentage (β=2.51, 95% CI 0.35 to 4.67, p=0.02) and conference attendance (β=2.70, 95% CI 0.11 to 5.29, p=0.04). Conclusions This study revealed favourable validity evidence for CD-RISC 10 and GRIT-S among IM residents. Residents demonstrated resilience within a competitive training environment despite less favourable test performance and grittiness that was manifested by completing tasks. This initial validity study provides a foundation for further research on resilience and grit among physicians in training.

Abstract Background: Continuing medical education (CME) often uses passive educational models including lectures. However, numerous studies have questioned the effectiveness of these less engaging educational strategies. Studies outside of CME suggest that engaged learning is associated with improved educational outcomes. However, measuring participants’ engagement can be challenging. We developed and determined the validity evidence for a novel instrument to assess learner engagement in CME.Methods: We conducted a cross-sectional validation study at a large, didactic-style CME conference. Content validity evidence was established through review of literature and previously published engagement scales and conceptual frameworks on engagement, along with an iterative process involving experts in the field, to develop an eight-item Learner Engagement Instrument (LEI). Response process validity was established by vetting LEI items on item clarity and perceived meaning prior to implementation, as well as using a well-developed online platform with clear instructions.. Internal structure validity evidence was based on factor analysis and calculating internal consistency reliability. Relations to other variables validity evidence was determined by examining associations between LEI and previously validated CME Teaching Effectiveness (CMETE) instrument scores. Following each presentation, all participants were invited to complete the LEI and the CMETE. Results: 51 out of 206 participants completed the LEI and CMETE (response rate 25%) Correlations between the LEI and the CMETE overall scores were strong (r=0.80). Internal consistency reliability for the LEI was excellent (Cronbach’s alpha=0.96). To support validity to internal structure, a factor analysis was performed and revealed a two dimensional instrument consisting of internal and external engagement domains. The internal consistency reliabilities were 0.96 for the internal engagement domain and 0.95 for the external engagement domain.Conclusion: Engagement, as measured by the LEI, is strongly related to teaching effectiveness. The LEI is supported by robust validity evidence including content, response process, internal structure, and relations to other variables. Given the relationship between learner engagement and teaching effectiveness, identifying more engaging and interactive methods for teaching in CME is recommended.

Abstract Background Owing to patient intolerance or drug interactions, alternative agents to rifampin are needed for management of staphylococcal periprosthetic joint infection. In the current study, we evaluated rifabutin, rifapentine and rifampin, with and without vancomycin, in a rat model of foreign body osteomyelitis. Methods Proximal tibiae were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and a Kirschner wire (K-wire) implanted in each. After 4 weeks of infection, rifampin, rifabutin, or rifapentine were administered, alone or with vancomycin. Tibiae and K-wires were cultured, and medians were reported as log10 colony-forming units (CFUs) per gram of bone or log10 CFUs per K-wire, respectively. Results Rifampin, rifabutin or rifapentine administered with vancomycin yielded less MRSA from bones (0.10, 3.02, and 0.10 log10 CFUs/g, respectively) than did no treatment (4.36 log10 CFUs/g) or vancomycin alone (4.64 log10 CFUs/g) (both P ≤ .02). The K-wires of animals receiving no treatment or vancomycin monotherapy recovered medians of 1.76 and 2.91 log10 CFUs/g per K-wire, respectively. In contrast, rifampin, rifabutin and rifapentine administered with vancomycin yielded medians of 0.1 log10 CFUs per K-wire, respectively. Rifampin resistance was detected in a single animal in the rifampin monotherapy group. Conclusions Rifabutin or rifapentine with vancomycin were as active as rifampin with vancomycin against MRSA in rat foreign body osteomyelitis, suggesting that rifabutin and/or rifapentine may be alternatives to rifampin in the clinical management of staphylococcal periprosthetic joint infections.

Abstract Background Continuing medical education (CME) often uses passive educational models including lectures. However, numerous studies have questioned the effectiveness of these less engaging educational strategies. Studies outside of CME suggest that engaged learning is associated with improved educational outcomes. However, measuring participants’ engagement can be challenging. We developed and determined the validity evidence for a novel instrument to assess learner engagement in CME. Methods We conducted a cross-sectional validation study at a large, didactic-style CME conference. Content validity evidence was established through review of literature and previously published engagement scales and conceptual frameworks on engagement, along with an iterative process involving experts in the field, to develop an eight-item Learner Engagement Instrument (LEI). Response process validity was established by vetting LEI items on item clarity and perceived meaning prior to implementation, as well as using a well-developed online platform with clear instructions. All item responses were double-coded for statistical analysis, using a dedicated survey research center. Internal structure validity evidence was based on factor analysis and calculating internal consistency reliability. Relations to other variables validity evidence was determined by examining associations between LEI and previously validated CME Teaching Effectiveness (CMETE) instrument scores. Following each presentation, all participants were invited to complete the LEI and the CMETE. Results A total of 2486 LEI and CMETE surveys were submitted during the 5-day course. Correlations between the LEI and the CMETE overall scores were strong (r = 0.80). Internal consistency reliability for the LEI was excellent (Cronbach’s alpha = 0.96). To support validity to internal structure, a factor analysis was performed and revealed a two dimensional instrument consisting of internal and external engagement domains. The internal consistency reliabilities were 0.96 for the internal engagement domain and 0.95 for the external engagement domain. Conclusion Engagement, as measured by the LEI, is strongly related to teaching effectiveness. The LEI is supported by robust validity evidence including content, response process, internal structure, and relations to other variables. Given the relationship between learner engagement and teaching effectiveness, identifying more engaging and interactive methods for teaching in CME is recommended.