Faculty Bibliography

Study Objectives: To help address the growing opioid overdose epidemic and help teach a core toxicological emergency, the authors taught the use of naloxone as an antidote to an opioid overdose, for all first-year medical students as a part of first responder training using cardiopulmonary resuscitation, as an online and in-person training over three years. Previously we demonstrated that in-person opioid overdose prevention training as an adjunct to BLST improves knowledge and preparedness. To compare the educational outcomes; knowledge, preparedness, and attitudes, for online vs in-person opioid overdose prevention training. Methods: Opioid overdose prevention trainings were conducted in person in 2014 and 2015, and online in 2016. First year students completed pre-and post-training surveys covering three measures: knowledge (11-point scale), attitudes (66-point scale) towards patients with opioid use disorders, and self-reported preparedness (60-point scale) to respond to an opioid overdose. Online and in-person scores across all three measures were compared using analysis of covariance (ANCOVA) methods across two years of trainings. Results: After controlling for pre-test scores, there were very small and not meaningful differences in attitude and knowledge scores between in-person training and online training. The estimated difference for knowledge was-0.06 (95% CI-0.48-0.35) and for attitudes was 0.64 (95% CI-0.22-1.50). The average scores related to preparedness were higher for the students who took the course online, estimated at 2.10 points (95% CI 0.97-3.22). Feedback was generally positive, with 96% of the in-person group saying future classes should receive the training and 95% of the online group saying all medical schools should provide the training. Conclusions: Online training has become a more common method of medical education due to its many advantages including standardization, scalability and flexibility to accommodate asynchronous learning. However, few studies have performed analyses of online training vs in-person training for relative effectiveness. The authors have demonstrated that for training medical students to administer naloxone as an antidote to an opioid overdose, online training is comparable to in-person training. These results support the use of online training for adding training on administering naloxone

Although the field of frailty research has expanded rapidly, it is still a nascent concept within the clinical specialties. Frailty, conceptualized as greater vulnerability to stressors because of significant depletion of physiological reserves, predicts poorer outcomes in several medical specialties, including cardiology, human immunodeficiency virus care, and nephrology, and in the behavioral and social sciences. Lack of a consensus definition, proliferation of measurement tools, inadequate understanding of the biology of frailty, and lack of validated clinical algorithms for frail individuals hinders incorporation of frailty assessment and frailty research into the specialties. In 2015, the American Geriatrics Society, the National Institute on Aging (NIA), and the Alliance for Academic Internal Medicine held a conference for awardees of the NIA-sponsored Grants for Early Medical/Surgical Specialists Transition into Aging Research program to review the current state of knowledge regarding frailty in the subspecialties and to highlight examples of integrating frailty research into the medical specialties. Research questions to advance frailty research into specialty medicine are proposed.

Background: The association of peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness, with neurodegeneration in multiple sclerosis (MS) is well established. The potential relationship of the adjoining inner nuclear layer (INL) with inflammatory disease activity is less well understood. Objective: To investigate the longitudinal relationship of INL volume changes with inflammatory disease activity. Methods: In this longitudinal multi-center study, spectral-domain optical coherence tomography (OCT) and clinical data were collected in 821 patients with MS, from eleven MS centres between 2010 and 2017. All patients had at least two visits (minimum follow- up of 6 months). Clinical data included EDSS score, occurring of relapses, including MS-associated optic neuritis (MSON). At each centre, automated segmentation of OCT scans was performed to obtain data on the pRNFL, GCIPL and INL. Annualized changes were calculated and generalized estimation equations were used to analyze longitudinal changes and associations with clinical measures. Results: In total, 1596 eyes from 798 patients (68.2% female), with a disease duration of 9.4 (+/-8.9) years, were included. Mean follow up duration was 2.3 years (range 0.5 to 5.2 years). Microcystic macular oedema (MMO) was present in 1.3% of eyes (20/1299 eyes). Clinical relapses other than MSON were present in 24.9% of patients, and disease progression was observed in 30.1%. In eyes with an episode of MSON during follow-up (N=61/1584), INL volume showed a significant increase over time (DELTAINL=0.01 mm3, p< 0.001), whereas in eyes without MSON during followup, no significant change in INL was observed (DELTAINL=0.00, p=0.308). Increase in INL volume in MSON eyes was related to a decrease in GCIPL volume (beta=-2.6, p=0.006). In eyes with MMO, the INL volume at the last visit was 0.06 mm3 higher compared to eyes without (p=0.003). There was no significant association between clinical relapses other than MSON, and INL volume changes (DELTAINL=0.00 mm3, p=0.773). Likewise, an in-or decrease in INL volume was independent of change of the EDSS score (OR=1.16, p=0.293, 95% CI 0.88-1.52). Conclusion: Our data demonstrate that an increase of the INL volume is associated with adjacent inflammation of the optic nerve and retina, but not with global physical disability. Therefore INL volume changes may be considered as a secondary outcome measure for anti-inflammatory treatment in MSON trials

Background: Retinal imaging by optical coherence tomography (OCT) has gained increasing attention in multiple sclerosis and other neuroinflammatory and neurodegenerative disorders. Ambiguous and incomplete reporting of methodology and OCT-derived data have limited the ability to compare data and to apply and generalize findings in the past. To improve this situation, the Advised Protocol for Optical coherence tomography Study Terminology and Elements (APOSTEL) recommendations have been developed to outline core information to be provided when reporting quantitative OCT studies with help of a 9-point checklist (Cruz-Herranz and Balk et al., Neurology 2016). The APOSTEL recommendations currently have the evidence level of an expert opinion (Class IV). Objective: To advance the APOSTEL recommendations for OCT reporting in a formalized procedure towards evidence-based guidelines. Methods: Studies reporting quantitative OCT results published within the last 24 months have been identified by a Pubmed search. The corresponding authors of these 1472 articles will be contacted and asked to participate in an online survey to evaluate and give feedback on the initial APOSTEL recommendations. The feedback obtained will be anonymized and distributed to a panel of international experts for evaluation and revision of the recommendations. After the initial round the corresponding authors who gave feedback will be informed about the intermediate results and asked to participate in the survey for a second time. This procedure will be repeated if necessary following the consensus-building procedure of a DELPHI process. To this end, for each round the feedback obtained as well as any revisions made to the APOSTEL recommendations will be summarized and questionnaires will be used for evaluation in order to reach consensus and to develop evidencebased guidelines for prospective OCT studies. Results: The degree of consensus of the survey's participants will be reported for the initial and the revised versions of the recommendations as well as the revisions made to the initial version. Conclusion: Formal guidelines for the reporting of quantitative OCT studies will be presented as well as the process of how they were developed

This study investigates the test-retest reliability of a battery of executive function (EF) tasks with a specific interest in testing whether the method that is used to create a battery-wide score would result in differences in the apparent test-retest reliability of children's performance. A total of 188 4-year-olds completed a battery of computerized EF tasks twice across a period of approximately two weeks. Two different approaches were used to create a score that indexed children's overall performance on the battery-i.e., (1) the mean score of all completed tasks and (2) a factor score estimate which used confirmatory factor analysis (CFA). Pearson and intra-class correlations were used to investigate the test-retest reliability of individual EF tasks, as well as an overall battery score. Consistent with previous studies, the test-retest reliability of individual tasks was modest (rs approximately .60). The test-retest reliability of the overall battery scores differed depending on the scoring approach (rmean = .72; rfactor_score = .99). It is concluded that the children's performance on individual EF tasks exhibit modest levels of test-retest reliability. This underscores the importance of administering multiple tasks and aggregating performance across these tasks in order to improve precision of measurement. However, the specific strategy that is used has a large impact on the apparent test-retest reliability of the overall score. These results replicate our earlier findings and provide additional cautionary evidence against the routine use of factor analytic approaches for representing individual performance across a battery of EF tasks.

OBJECTIVE: To analyze the association between US urology department Twitter presence and U.S. News and World Report (USNWR) reputation scores, to examine the content, informational value, and intended audience of these platforms, and to identify objectives for Twitter use. METHODS: We identified Twitter accounts for the top 50 ranked hospitals for urology in the 2016-2017 USNWR. Correlation coefficients were calculated between Twitter metrics (number of followers, following, tweets, and Klout influence scores) with USNWR reputation scores. We also performed a detailed content analysis of urology department tweets during a 6 month period to characterize the content. Finally, we distributed a survey to the urology department accounts via Twitter inquiring who administers the content and their objectives for Twitter use. RESULTS: Among 42 scored urology departments with Twitter accounts, the median number of followers, following, and tweets were 337, 193 and 115, respectively. All of these Twitter metrics had a statistically significant positive correlation with reputation scores (p<0.05). Content analyses revealed that most tweets were about conferences, education, and publications, targeting the general public or urological community. Survey results revealed that the primary reason for twitter use among urology departments was visibility/reputation, and urologists are considered the most important target audience. CONCLUSIONS: There is statistically significant correlation between Twitter activity and USNWR reputation scores for urology departments. Our results suggest that Twitter provides a novel mechanism for urology departments to communicate about academic and educational topics, and social media engagement can enhance reputation.

Background: Emerging evidence suggests novel roles for bacterially derived vitamin K forms known as menaquinones in health and disease, which may be attributable in part to anti-inflammatory effects. However, the relevance of menaquinones produced by gut bacteria to vitamin K requirements and inflammation is undetermined.Objective: This study aimed to quantify fecal menaquinone concentrations and identify associations between fecal menaquinone concentrations and serum vitamin K concentrations, gut microbiota composition, and inflammation.Design: Fecal and serum menaquinone concentrations, fecal microbiota composition, and plasma and fecal cytokine concentrations were measured in 80 men and postmenopausal women (48 men, 32 women, age 40-65 y) enrolled in a randomized, parallel-arm, provided-food trial. After consuming a run-in diet for 2 wk, participants were randomly assigned to consume a whole grain-rich (WG) or a refined grain-based (RG) diet for 6 wk. Outcomes were measured at weeks 2 and 8.Results: The median total daily excretion of menaquinones in feces was 850 nmol/d but was highly variable (range: 64-5358 nmol/d). The total median (IQR) fecal concentrations of menaquinones decreased in the WG diet compared with the RG diet [-6.8 nmol/g (13.0 nmol/g) dry weight for WG compared with 1.8 nmol/g (12.3 nmol/g) dry weight for RG; P < 0.01)]. However, interindividual variability in fecal menaquinone concentrations partitioned individuals into 2 distinct groups based on interindividual differences in concentrations of different menaquinone forms rather than the diet group or the time point. The relative abundances of several gut bacteria taxa, Bacteroides and Prevotella in particular, differed between these groups, and 42% of identified genera were associated with ≥1 menaquinone form. Menaquinones were not detected in serum, and neither fecal concentrations of individual menaquinones nor the menaquinone group was associated with any marker of inflammation.Conclusion: Menaquinone concentrations in the human gut appear highly variable and are associated with gut microbiota composition. However, the health implications remain unclear. This trial was registered at clinicaltrials.gov as NCT01902394.

Little is known about how neighborhood noise influences cardiovascular disease (CVD) risk among low-income populations. The aim of this study was to investigate associations between neighborhood noise complaints and body mass index (BMI) and blood pressure (BP) among low-income housing residents in New York City (NYC), including the use of global positioning system (GPS) data. Data came from the NYC Low-Income Housing, Neighborhoods and Health Study in 2014, including objectively measured BMI and BP data (N = 102, Black = 69%), and 1 week of GPS data. Noise reports from "NYC 311" were used to create a noise complaints density (unit: 1000 reports/km2) around participants' home and GPS-defined activity space neighborhoods. In fully-adjusted models, we examined associations of noise complaints density with BMI (kg/m2), and systolic and diastolic BP (mmHg), controlling for individual- and neighborhood-level socio-demographics. We found inverse relationships between home noise density and BMI (B = -2.7 [kg/m2], p = 0.009), and systolic BP (B = -5.3 mmHg, p = 0.008) in the fully-adjusted models, and diastolic BP (B = -3.9 mmHg, p = 0.013) in age-adjusted models. Using GPS-defined activity space neighborhoods, we observed inverse associations between noise density and systolic BP (B = -10.3 mmHg, p = 0.019) in fully-adjusted models and diastolic BP (B = -7.5 mmHg, p = 0.016) in age-adjusted model, but not with BMI. The inverse associations between neighborhood noise and CVD risk factors were unexpected. Further investigation is needed to determine if these results are affected by unobserved confounding (e.g., variations in walkability). Examining how noise could be related to CVD risk could inform effective neighborhood intervention programs for CVD risk reduction.

Introduction: The optic nerve and visual pathway are frequent sites for involvement in multiple sclerosis (MS). Optical coherence tomography (OCT) detects retinal nerve fiber layer (RNFL) thinning in eyes of patients with MS or in the case of clinically-or radiologically-isolated syndromes. Current diagnostic criteria do not include the optic nerve as an imaging lesion site despite a high prevalence of acute optic neuritis (ON) among early MS and clinically isolated syndrome (CIS) patients. We sought to determine optimal thresholds for inter-eye difference in RNFL thickness that are most predictive of an optic nerve lesion. Methods: Spectral-domain (SD-)OCT data from an ongoing collaborative study of visual outcomes in MS were analyzed for a single site. Median values for inter-eye difference in RNFL thickness were also calculated from the RENEW trial cohort at the 6-month endpoint. RENEW was a randomized, placebo-controlled trial of opicinumab in subjects with a first episode of acute unilateral ON, and represents the most well-characterized cohort of CIS patients with ON incorporating modern tests of visual structure and function. RENEW utilized SD-OCT with a centralized reading center. Results: Among healthy volunteer control participants in the collaborative investigation (convenience sample, n=31), the 95th percentile value for inter-eye difference (upper boundary of expected for normals) was 6.0 microns. This value, as well as median intereye differences from the RENEW cohort (8.5 microns for placebo, n=41; 13.0 microns for opicinumab, n=41), were applied to convenience sample group of MS patients (n=136) as a validation cohort. Positive predictive value, sensitivity and specificity for identifying MS patients with a history of unilateral ON were greatest for the 6-micron value compared to the RENEW medians in a 2x2 table analysis (p< 0.0001, chi-square). The 6-micron threshold was also predictive of worse binocular low-contrast acuity at 2.5% (p=0.02) and 1.25% (p=0.002, linear regression). ROC curve analysis demonstrated an optimal inter-eye difference threshold of 5 microns for identifying unilateral ON in the MS cohort. Conclusion: Inter-eye differences of 5-6 microns in RNFL thickness are thus far optimal for predicting a unilateral optic nerve lesion in MS. Larger international collaborative investigations involving 20 or more MS validation cohort sites are underway to maximize precision and generalizability for these OCT-based thresholds

BACKGROUND:Heart failure is one of the most important complications of chronic kidney disease (CKD). However, few studies comprehensively investigated left ventricular (LV) structure and function in relation to 2 key CKD measures, estimated glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (ACR). METHODS AND RESULTS/RESULTS:=0.010]). Dichotomizing echo parameters with clinical thresholds, the stronger relationships of ACR over eGFR were further evident. CONCLUSIONS:LV mass was related to both CKD measures, whereas LV size and function were robustly associated with albuminuria. These results have implications for pathophysiological processes behind cardiorenal syndrome and targeted cardiac assessment in patients with CKD.