Kevin A. Buhr

Training Mentors of Clinical and Translational Research Scholars: A Randomized Controlled Trial

Purpose To determine whether a structured mentoring curriculum improves research mentoring skills. Method The authors conducted a randomized controlled trial (RCT) at 16 academic health centers (June 2010 to July 2011). Faculty mentors of trainees who were conducting clinical/translational research ≥50% of the time were eligible. The intervention was an eight-hour, case-based curriculum focused on six mentoring competencies. The primary outcome was the change in mentors’ self-reported pretest to posttest composite scores on the Mentoring Competency Assessment (MCA). Secondary outcomes included changes in the following: mentors’ awareness as measured by their self-reported retrospective change in MCA scores, mentees’ ratings of their mentors’ competency as measured by MCA scores, and mentoring behaviors as reported by mentors and their mentees. Results A total of 283 mentor–mentee pairs were enrolled: 144 mentors were randomized to the intervention; 139 to the control condition. Self-reported pre-/posttest change in MCA composite scores was higher for mentors in the intervention group compared with controls (P < .001). Retrospective changes in MCA composite scores between the two groups were even greater, and extended to all six subscale scores (P < .001). More intervention-group mentors reported changes in their mentoring practices than control mentors (P < .001). Mentees working with intervention-group mentors reported larger changes in retrospective MCA pre-/posttest scores (P = .003) and more changes in their mentors’ behavior (P = .002) than those paired with control mentors. Conclusions This RCT demonstrates that a competency-based research mentor training program can improve mentors’ skills.

Leveraging Electronic Health Record Systems to Create and Provide Electronic Cancer Survivorship Care Plans: A Pilot Study

PURPOSE The Institute of Medicine (IOM) recommends cancer survivors receive survivorship care plans after completing active cancer treatment. However, care plan creation requires significant time and effort, contributing to diminished adoption of this recommendation. Electronic health record (EHR) systems have been proposed as a solution. We assessed the feasibility of creating and delivering care plans within an EHR system. METHODS Thirty-eight breast cancer survivors without existing care plans were recruited during a follow-up visit to their primary oncologist. Using an EHR template, an oncologist created an individualized care plan for each participant. Time spent creating each plan was recorded. Participant use and feedback were collected. RESULTS Participants enrolled a median of 19.7 months after diagnosis (range, 4.3 to 57 months). A minority of IOM-recommended plan elements could be automatically imported without any manual entry. The majority of elements required interpretation and manual import by the clinician. However, with an established infrastructure for importing elements, the time needed to create a care plan electronically was short (median, 3 minutes; range 2 to 12 minutes). Most survivors (n = 36; 95%) successfully accessed their care plans online and spent a median of 12 minutes (range, 0.5 to 61.9 minutes) reviewing them. Survivors perceived the plans as useful and did not generally report difficulty in accessing them online or understanding content. CONCLUSION Rapid care plan creation and delivery within an EHR is possible. Plans were available to all (survivors, oncologists, primary care physicians) via the EHR. Further research is required to explore the barriers to automating data importation into plans as well as the impact of EHR-integrated plans.

The concept of precision extended to the atherogenic index of plasma.

BACKGROUND The atherogenic index of plasma (AIP), defined as the base 10 logarithm of the ratio of plasma triglyceride (TG) to high density lipoprotein cholesterol (HDL-C), has been employed as a predictor of cardiovascular risk. We seek to quantify the analytical precision of the AIP using the coefficients of variation (CVs) of the TG and HDL-C assays. METHODS Error propagation methods are employed to develop a simple formula for the standard deviation of the random analytical error in the AIP assuming that the errors in the TG and HDL-C assays are normally distributed. An alternative derivation assuming log-normal distribution of errors gives nearly identical results while avoiding subtle technical problems. RESULTS The SD of the AIP is given by sigma(AIP) approximately = 1/ln(10) square root(CV(TG)(2) + CV(HDL-C)(2)) and this formula will provide SD results that are accurate within 0.4% for CVs of TG and HDL-C less than 5%, as compared with results of Monte Carlo simulation. We also explain that the concept of CV cannot be applied to the AIP since it is a logarithm. CONCLUSIONS The formula provides a simple means to quantify the precision of the AIP from precision data available for the TG or HDL-C assays.

Relationships Between Biomechanics, Tendon Pathology, and Function in Individuals With Lateral Epicondylosis

STUDY DESIGN Single-cohort descriptive and correlational study. OBJECTIVES To investigate the relationships between tendon pathology, biomechanical measures, and self-reported pain and function in individuals with chronic lateral epicondylosis. BACKGROUND Lateral epicondylosis has a multifactorial etiology and its pathophysiology is not well understood. Consequently, treatment remains challenging, and lateral epicondylosis is prone to recurrence. While tendon pathology, pain system changes, and motor impairments due to lateral epicondylosis are considered related, their relationships have not been thoroughly investigated. METHODS Twenty-six participants with either unilateral (n = 11) or bilateral (n = 15) chronic lateral epicondylosis participated in this study. Biomechanical measures (grip strength, rate of force development, and electromechanical delay) and measures of tendon pathology (magnetic resonance imaging and ultrasound) and self-reported pain and function (Patient-Rated Tennis Elbow Evaluation) were performed. Partial Spearman correlations, adjusting for covariates (age, gender, weight, and height), were used to evaluate the relationship between self-reported pain, function, and biomechanical and tendon pathology measures. RESULTS Statistically significant correlations between biomechanical measures and the Patient-Rated Tennis Elbow Evaluation ranged in magnitude from 0.44 to 0.68 (P<.05); however, no significant correlation was observed between tendon pathology (magnetic resonance imaging and ultrasound) measures and the Patient-Rated Tennis Elbow Evaluation (r = -0.02 to 0.31, P>.05). Rate of force development had a stronger correlation (r = 0.54-0.68, P<.05) with self-reported function score than with grip strength (r = 0.35-0.47, P<.05) or electromechanical delay (r = 0.5, P<.05). CONCLUSION Biomechanical measures (pain-free grip strength, rate of force development, electromechanical delay) have the potential to be used as outcome measures to monitor progress in lateral epicondylosis. In comparison, the imaging measures (magnetic resonance imaging and ultrasound) were useful for visualizing the pathophysiology of lateral epicondylosis. However, the severity of the pathophysiology was not related to pain and function, indicating that imaging measures may not provide the best clinical assessment.

Effect of Lateral Epicondylosis on Grip Force Development

STUDY DESIGN Case-Control. INTRODUCTION Although it is well known that grip strength is adversely affected by lateral epicondylosis (LE), the effect of LE on rapid grip force generation is unclear. PURPOSE OF THE STUDY To evaluate the effect of LE on the ability to rapidly generate grip force. METHODS Twenty-eight participants with LE (13 unilateral and 15 bilateral LE) and 13 healthy controls participated in this study. A multiaxis profile dynamometer was used to evaluate grip strength and rapid grip force generation. The ability to rapidly produce force is composed of the electromechanical delay and rate of force development. Electromechanical delay is defined as the time between the onset of electrical activity and the onset of muscle force production. The Patient-rated Tennis Elbow Evaluation (PRTEE) questionnaire was used to assess pain and functional disability. Magnetic resonance imaging was used to evaluate tendon degeneration. RESULTS LE-injured upper extremities had lower rate of force development (50 lb/sec, confidence interval [CI]: 17, 84) and less grip strength (7.8 lb, CI: 3.3, 12.4) than nonnjured extremities. Participants in the LE group had a longer electromechanical delay (- 59% , CI: 29, 97) than controls. Peak rate of force development had a higher correlation (r = 0.56; p<0.05) with PRTEE function than grip strength (r = 0.47; p<0.05) and electromechanical delay (r = 0.30; p>0.05) for participants with LE. In addition to a reduction in grip strength, those with LE had a reduction in rate of force development and an increase in electromechanical delay. CONCLUSIONS Collectively, these changes may contribute to an increase in reaction time, which may affect risk for recurrent symptoms. These findings suggest that therapists may need to address both strength and rapid force development deficits in patients with LE. LEVEL OF EVIDENCE 3B.

Daptomycin Dosing Based on Ideal Body Weight versus Actual Body Weight: Comparison of Clinical Outcomes

ABSTRACT Daptomycin use at our institution changed to ideal body weight dosing based on a published analysis of pharmacokinetic-pharmacodynamic efficacy target attainment, bacterial ecology, and a desire to reduce drug toxicity. The current study compared outcomes between actual body weight and ideal body weight dosing of daptomycin before and after this intervention. In the evaluable group, 69 patients received doses based on actual body weight and 48 patients received doses based on ideal body weight. Patients were treated for documented Enterococcus species, Staphylococcus aureus, or coagulase-negative Staphylococcus infections, including bloodstream, intraabdominal, skin and soft tissue, urinary, and bone. There was no statistically significant difference in clinical success between the groups (88.9% for actual body weight compared to 89.1% for ideal body weight, P = 0.97). After we adjusted for gender, age, body mass index, concomitant 3-hydroxy-3-methylglutaryl–coenzyme A reductase inhibitors, infection type, and organism type, clinical success rates remained similar between groups (adjusted odds ratio of 0.68 in favor of actual body weight, 95% confidence interval [CI] of 0.13 to 3.55). Microbiological outcomes, length of stay, mortality, and adverse effects were also similar between groups. Further studies are warranted to confirm that ideal body weight dosing provides similar outcomes to actual body weight dosing for all patients and types of infections and organisms.

The effect of lateral epicondylosis on upper limb mechanical parameters

BACKGROUND Lateral epicondylosis is a prevalent and costly musculoskeletal disorder characterized by degeneration of the common extensor tendon origin at the lateral epicondyle. Grip strength is commonly affected due to lateral epicondylosis. However, less is known about the effect of lateral epicondylosis on other functional parameters such as ability to react to rapid loading. METHODS Twenty-nine lateral epicondylosis participants and ten controls participated in a case-control study comparing mechanical parameters (mass, stiffness and damping), magnetic resonance imaging signal intensity and grip strength of injured and uninjured limbs. A mixed effects model was used to assess the effect of dominance and injury on mechanical parameters and grip strength. FINDINGS Significant effect of injury and dominance was observed on stiffness, damping and grip strength. An injured upper limb had, on average, 18% less stiffness (P<0.01, 95% CI [9.8%, 26%]), 21% less damping (P<0.01, 95% CI [11%, 31%]) and 50% less grip strength (P<0.01, 95% CI [37%, 61%]) than an uninjured upper limb. The dominant limb had on average 15% more stiffness (P<0.01, 95% CI [8.0%, 23%], 33% more damping (P<0.01, 95% CI [22%, 45%]), and 24% more grip strength (P<0.01, 95% CI [6.6%, 44%]) than the non-dominant limb. INTERPRETATION Lower mechanical parameters are indicative of a lower capacity to oppose rapidly rising forces and quantify an important aspect of upper limb function. For individuals engaged in manual or repetitive activities involving the upper limb, a reduction in ability to oppose these forces may result in increased risk for injury or recurrence.

β-AR polymorphisms and glycemic and lipid parameters in hypertensive individuals receiving carvedilol or metoprolol.

BACKGROUND β-Blocker therapy and β-adrenergic receptor (β-AR) polymorphisms are associated with increases in glucose and lipid levels. We investigated associations of common β1 and β2-AR single-nucleotide polymorphisms (SNPs) with metabolic and lipid variables, and examined interactions with β-blocker treatment assignment to affect these parameters. METHODS This was a post hoc analysis of a double-blinded clinical trial of nondiabetic, hypertensive individuals that were randomized to receive carvedilol or metoprolol succinate. Fasting glucose, insulin, and lipid levels were measured at baseline, 3 months, and after 6 months. Genotypes for β1-AR SNPs Ser49Gly & Gly389Arg and β2-AR Arg16Gly & Gln27Glu were determined. Multivariable mixed models were used to examine associations between β-AR polymorphisms, metabolic parameters, and SNP interactions with β-blocker therapy (p(interaction)). RESULTS The 322 subjects were mean (s.d.) 51.5 (11.2) years old. After 6 months, insulin levels increased by 35.6% on metoprolol and 9.9% on carvedilol (P = 0.015). In univariate models, the Gln27Gln genotype had higher overall insulin levels with β-blockade compared to the Glu27Glu genotype (P = 0.006). Both Arg16Gly (P = 0.012) and Gln27Glu (P = 0.037) SNPs were associated with higher triglycerides levels. An interaction between the Arg16Gly SNP and treatment was identified (p(int) = 0.048). CONCLUSIONS These data suggest that insulin and triglycerides may be influenced by β2-AR polymorphisms in patients taking β blockers.

Surrogate End Points in Secondary Analyses of Cardiovascular Trials

A surrogate end point is one that is used as a substitute for a clinical end point of more direct interest, usually for reasons of practicality, and that is expected to predict clinical benefit. Surrogate end points play a critical role in the advancement of all medical research, and cardiovascular (CV) research in particular. However, the relationship between a surrogate end point and its clinical end point is usually complex, and there are many examples where results based on surrogates have proved to be misleading. Secondary analyses of existing clinical trial data are likely to involve surrogate end points, if only because clinical end points will have been extensively studied as part of the primary analysis of a trial large enough to collect useful clinical end point data. Validation of a surrogate end point is a laudable goal for a secondary analysis of a large clinical end point trial (or meta-analysis of multiple smaller trials), and the result may be an important new tool for further study of a class of compounds in a particular disease context. Secondary analyses using surrogate end points may also provide new insight into disease or treatment mechanism, but as with any surrogate end point analysis, the results can mislead, and the existing literature is heavy on application and light on methodology. Surrogate end points often substitute efficiency for clarity, and while many interesting and potentially informative secondary analyses of CV trials will involve surrogates, results are likely to be ambiguous and should be interpreted with care.

Age-dependent reference intervals for measured bioavailable testosterone on the Siemens Advia Centaur: ethnicity-specific values not necessary for South Asians.

OBJECTIVES To determine reference intervals for bioavailable testosterone for the Siemens Centaur analyzer and to assess the need for ethnicity-specific ranges for total testosterone and/or bioavailable testosterone in South Asians. DESIGN AND METHODS Testosterone was measured before and after ammonium sulphate precipitation on specimens collected from a small cohort of healthy male South Asians and Europeans. RESULTS Inter-ethnicity differences in BioT and TT were not significant. Age-specific BioT reference intervals are reported. CONCLUSIONS Ethnicity-specific TT and BioT reference intervals for South Asians do not appear necessary.