Neurology Clerkship: Predictors of Objective Structured Clinical Examination and Shelf Performance.

BACKGROUND: We sought to determine whether the following factors are associated with stronger performance on the medical school neurology clerkship: (1) structure of the outpatient rotation (working with a single general neurologist or multiple subspecialists), (2) dedicated shelf exam preparation, and (3) clerkships completed prior to neurology rotation. METHODS: A total of 439 Feinberg medical students between 2014 and 2016 were analyzed based on the 3 variables of interest listed above. Student performance was evaluated using the National Board of Medical Examiner shelf exam and Objective Structured Clinical Examination/standardized evaluation scores. Univariate and multivariate analyses were conducted. RESULTS: The format of the 2-week outpatient rotation did not significantly affect shelf examination (P = .59), or standardized evaluation (P = .34) scores. Taking a shelf pre-test correlated with overall higher standardized evaluation scores (P < .01), and higher shelf examination scores (P < .01). No individual clerkship correlated with better performance; however, the total number of core clerkships was associated with higher shelf examination scores (P = .007). Each additional core clerkship taken prior to neurology was associated with 0.72 points greater shelf examination score. CONCLUSIONS: Greater attending continuity did not appear to be associated with stronger performance perhaps due to a difference in types of cases observed. Students who took a practice shelf exam did better on both their shelf exam and standardized evaluation, suggesting that acquisition of knowledge translates to a better clinical performance. No individual clerkship offers an advantage, but rather it is the total number of clerkships that is correlated with stronger performance.

Choosing an imbalance metric for covariate-constrained randomization in multiple-arm cluster-randomized trials.

BACKGROUND: In cluster-randomized controlled trials (C-RCTs), covariate-constrained randomization (CCR) methods efficiently control imbalance in multiple baseline cluster-level variables, but the choice of imbalance metric to define the subset of "adequately balanced" possible allocation schemes for C-RCTs involving more than two arms and continuous variables is unclear. In an ongoing three-armed C-RCT, we chose the min(three Kruskal-Wallis [KW] test P values) > 0.30 as our metric. We use simulation studies to explore the performance of this and other metrics of baseline variable imbalance in CCR. METHODS: We simulated three continuous variables across three arms under varying allocation ratios and assumptions. We compared the performance of min(analysis of variance [ANOVA] P value) > 0.30, min(KW P value) > 0.30, multivariate analysis of variance (MANOVA) P value > 0.30, min(nine possible t test P values) > 0.30, and min(Wilcoxon rank-sum [WRS] P values) > 0.30. RESULTS: Pairwise comparison metrics (t test and WRS) tended to be the most conservative, providing the smallest subset of allocation schemes (10%-13%) meeting criteria for acceptable balance. Sensitivity of the min(t test P values) > 0.30 for detecting non-trivial imbalance was 100% for both hypothetical and resampled simulation scenarios. The KW criterion maintained higher sensitivity than both the MANOVA and ANOVA criteria (89% to over 99%) but was not as sensitive as pairwise criteria. CONCLUSIONS: Our criterion, the KW P value > 0.30, to signify "acceptable" balance was not the most conservative, but it appropriately identified imbalance in the majority of simulations. Since all are related, CCR algorithms involving any of these imbalance metrics for continuous baseline variables will ensure robust simultaneous control over multiple continuous baseline variables, but we recommend care in determining the threshold of "acceptable" levels of (im)balance. TRIAL REGISTRATION: This trial is registered on ClinicalTrials.gov (initial post: December 1, 2016; identifier: NCT02979444 ).

Impact of Real-Time Clinical Decision Support on Blood Utilization and Outcomes in Hospitalized Patients with Solid Tumor Cancer.

INTRODUCTION: Patients with cancer are frequently hospitalized, and anemia is a common complication of cancer care. Transfusion is often required and commonly occurs above guideline-supported thresholds. It was hypothesized that an educational intervention, combined with real-time clinical decision support (CDS), would reduce blood utilization among hospitalized solid tumor cancer patients without adversely affecting outcomes. METHODS: A retrospective, historical control analysis was conducted comparing transfusion utilization among hospitalized solid tumor cancer patients before and after implementation of the educational intervention and CDS. The primary outcome was receipt of red blood cell (RBC) transfusion. Secondary outcomes included total RBC transfusions per 100 inpatient-days, readmission, outpatient transfusion within seven days of discharge, inpatient mortality, and odds of transfer to the ICU. RESULTS: The odds of receiving a transfusion were significantly reduced in the postintervention cohort (odds ratio [OR] = 0.52, p = 0.005). Among patients receiving transfusion, there was no significant difference between groups in the number of RBC transfusions per 100 inpatient-days (incidence rate ratio = 0.87, p = 0.26). There were also no significant differences in readmission, outpatient transfusion within seven days of discharge, or inpatient mortality, though patients in the postintervention cohort had lower odds of ICU transfer (OR = 0.29, p = 0.04). CONCLUSION: The combined use of an educational intervention and CDS in a hospitalized solid tumor cancer patient population was associated with lower blood utilization, similar patient outcomes, and unchanged short-term outpatient transfusion requirements. Hospitals should consider similar interventions to work toward appropriate resource allocation and mitigation of transfusion-associated risk in this patient population.

Physical Activity and Worsening of Radiographic Findings in Persons With or at Higher Risk of Knee Osteoarthritis.

OBJECTIVE: The benefits of physical activity among persons with or at higher risk for knee osteoarthritis are well established. However, activity levels in this population are low, in part due to concern that activity will damage the knee joint. We hypothesized that sedentary and moderate-vigorous physical activity are each associated with greater risk of radiographic worsening of knee OA. METHODS: In Osteoarthritis Initiative participants with or at higher risk for knee OA enrolled in an accelerometer substudy at 48 months (study baseline), physical activity was measured by a uniaxial accelerometer (ActiGraph GT1M). Radiographic progression was defined as any 48 month to 96 month worsening of Kellgren/Lawrence (K/L) grade scores. All analyses were knee-level; we used multivariable logistic regression with generalized estimating equations, adjusting for key covariates. RESULTS: Of the 1,206 participants, 631 (52%) were female, the mean ± SD age was 64 ± 9 years, and mean ± SD body mass index (BMI) was 28 ± 5. The mean ± SD average daily sedentary activity was 602 ± 86 minutes, average daily light activity was 284 ± 75 minutes, and average daily moderate-vigorous activity was 20 ± 20 minutes. In 1,978 knees, 267 (14%) had worsening of K/L grade scores. In the multivariable model, age, sex, BMI, and pain, were associated with K/L grade worsening, but neither sedentary activity (adjusted odds ratio [OR] 0.99 [95% confidence interval (95% CI) 0.97-1.01]) nor moderate-vigorous activity (adjusted OR 1.00 [95% CI 0.91-1.09]) were associated with K/L grade worsening. CONCLUSION: In persons with or at higher risk for knee OA, age, sex, BMI, and pain, but not objectively measured average daily minutes of sedentary or moderate-vigorous activity, were associated with subsequent worsening of K/L grade. Whether findings differ in persons with more severe knee OA and/or engaged more frequently in moderate-vigorous activity should be examined in future studies.

Performance of Forced Vital Capacity and Lung Diffusion Cutpoints for Associated Radiographic Interstitial Lung Disease in Systemic Sclerosis.

OBJECTIVE: Forced vital capacity (FVC) and DLCO are used for screening of systemic sclerosis-associated interstitial lung disease (SSc-ILD). The study purpose was to determine the sensitivity, specificity, and negative predictive value (NPV) (proportion of true negative screening tests) of FVC and DLCO thresholds for SSc-ILD on chest high-resolution computed tomography (HRCT) scans. METHODS: Patients fulfilling American College of Rheumatology 2013 SSc criteria with a chest HRCT scan and pulmonary function tests (PFT) were studied. A thoracic radiologist quantified radiographic ILD. Optimal FVC and DLCO % predicted thresholds for ILD were identified using receiver-operating characteristic curves. The FVC and DLCO combinations with greatest sensitivity and specificity were also determined. Subanalysis was performed in patients with positive Scl-70 autoantibodies. RESULTS: The study included 265 patients. Of 188 (71%) with radiographic ILD, 59 (31%) had "normal" FVC (≥ 80% predicted), and 65 out of 151 (43%) had "normal" DLCO (≥ 60% predicted). FVC < 80% (sensitivity 0.69, specificity 0.73), and DLCO < 62% (sensitivity 0.60, specificity 0.70) were optimal thresholds for radiographic SSc-ILD. All FVC and DLCO threshold combinations evaluated had NPV < 0.70. The NPV for radiographic ILD for FVC < 80% was lower in patients with positive Scl-70 autoantibody (NPV = 0.05) compared to negative Scl-70 autoantibody (NPV = 0.57). CONCLUSION: Radiographic ILD is prevalent in SSc despite "normal" PFT. No % predicted FVC or DLCO threshold combinations yielded high NPV for SSc-ILD screening. "Normal" FVC and DLCO in patients with SSc, especially those with positive Scl-70 autoantibodies, should not obviate consideration of HRCT for ILD evaluation.

Cord Blood Metabolites Associated with Newborn Adiposity and Hyperinsulinemia.

OBJECTIVE: To evaluate the association between cord blood amino acid and acylcarnitine profiles and measures of adiposity and hyperinsulinemia in healthy newborns. STUDY DESIGN: A cross-sectional study of 118 full-term infants born to mothers without gestational diabetes was performed. Cord blood leptin, C-peptide, acylcarnitine, and amino acid levels were measured. Body composition was measured by air displacement plethysmography. Multivariate linear regression and principal component analysis were used to analyze associations of cord blood metabolites with newborn anthropometrics, leptin, and C-peptide. RESULTS: Acylcarnitines AC C2, AC C4-DC/Ci4-DC, and AC C8:1-OH/C6:1-DC were positively associated with leptin, and AC C14, AC C14:2, AC C16, AC C18, and AC C18:2 were negatively associated with C-peptide (P ≤ .0016). Principal component analysis revealed a positive association between factor 1(AC C2, AC C3, AC C5, AC C4/Ci4, AC C4-OH, AC C4-DC/Ci4-DC, glutamate/glutamine, and glycine) and adiposity measures. CONCLUSIONS: The positive association of AC C2 and AC C4-DC/Ci4-DC levels with leptin may reflect excess fat stores, higher fatty acid oxidation rate, and mitochondrial dysfunction leading to accumulation of acylcarnitine intermediates. Principal component analysis revealed a positive association between branched chain amino acid and ketone body metabolites and adiposity, confirming prior findings in adults. Cord blood acylcarnitine profiles may identify at-risk children before obesity or insulin resistance develops.

The Impact of Family History on the Clinical Features of Huntington's Disease.

BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. In most cases the disease is inherited from a parent, although a considerable number of affected persons have no reported family history of the disease. While CAG repeat length is negatively correlated with age of symptom onset, variability exists suggesting that other variables may influence symptom onset. OBJECTIVES: The objective of this study is to determine whether awareness of a family history of HD has an impact on symptom onset and disease manifestations. METHODS: Data were obtained from Enroll-HD to compare subjects with a family history of HD to subjects without on various key clinical outcomes. In addition, multiple regressions were performed to investigate the impact of family history on the age at onset of depression and motor symptoms. RESULTS: 4,285 mutation positive subjects were included in the analysis, of which 4.81% had a negative family history. Controlling for CAG repeat length, a positive family history predicted an onset of depression 11.438 years earlier and an onset of motor symptoms 6.681 years earlier when compared to having a negative family history. Subjects with a positive family history were more likely to report behavioral manifestations as the initial major symptom of HD (38.6% vs. 29.6%, p = 0.023), and were more likely to report previous suicidal ideation/attempts (26.2% vs. 20.3%, p = 0.046). CONCLUSIONS: A positive family history of HD appears to be associated with an earlier onset of depression and overall disease manifestations. Implications regarding the role of genetic versus environmental contributions to symptom onset in HD are discussed.