Sandra C Bryant

Mayo Clinic - Rochester, Rochester, Minnesota, United States

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Publications (74)289.58 Total impact

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    ABSTRACT: Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare clinical syndrome associated with significant mortality. Although the use of plasma exchange (PE) in TA-TMA continues to be explored, evidence for its efficacy is debated. We performed a single institution, retrospective study to evaluate the efficacy of PE in treating TA-TMA patients. Special attention was given to efficacy in relation to the timing of presentation with TA-TMA since transplant. Thirty-three patients diagnosed with TA-TMA and treated with PE between January 1999 and December 2010 were included in the study. Clinical improvement was seen in eight patients (24%); four patients achieved complete resolution while the remaining four achieved partial resolution. All-cause day-30 and day-100 mortality was 33 and 55%, respectively. There was a trend toward a better outcome (complete/partial) for those presenting ≥ 100 days after transplantation (42%) vs. < 100 days after transplantation (14%; P-value = 0.15). Similarly, those presenting at ≥ 100 days had better, but not significantly, 30-day and 100-day all-cause mortality rates (17 and 33%, respectively) than those presenting at < 100 days (43 and 67%, respectively) (P-value = 0.25 and 0.08, for 30- and 100-day all-cause mortality, respectively). This is the first study looking at the efficacy of PE while considering the time of presentation since transplantation and is one of the largest single institution series of TA-TMA. The overall efficacy of PE is poor; however, patients who present with TA-TMA ≥100 days after transplant may have better outcome and lower mortality. J. Clin. Apheresis, 2014. © 2014 Wiley Periodicals, Inc.
    Journal of Clinical Apheresis 09/2014; · 2.27 Impact Factor
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    ABSTRACT: Context.- Systems-based practice (SBP) is 1 of 6 core competencies required in all resident training programs accredited by the Accreditation Council for Graduate Medical Education. Reliable methods of assessing resident competency in SBP have not been described in the medical literature. Objective.- To develop and validate an analytic grading rubric to assess pathology residents' analyses of SBP problems in clinical chemistry. Design.- Residents were assigned an SBP project based upon unmet clinical needs in the clinical chemistry laboratories. Using an iterative method, we created an analytic grading rubric based on critical thinking principles. Four faculty raters used the SBP project evaluation rubric to independently grade 11 residents' projects during their clinical chemistry rotations. Interrater reliability and Cronbach α were calculated to determine the reliability and validity of the rubric. Project mean scores and range were also assessed to determine whether the rubric differentiated resident critical thinking skills related to the SBP projects. Results.- Overall project scores ranged from 6.56 to 16.50 out of a possible 20 points. Cronbach α ranged from 0.91 to 0.96, indicating that the 4 rubric categories were internally consistent without significant overlap. Intraclass correlation coefficients ranged from 0.63 to 0.81, indicating moderate to strong interrater reliability. Conclusions.- We report development and statistical analysis of a novel SBP project evaluation rubric. The results indicate the rubric can be used to reliably assess pathology residents' critical thinking skills in SBP.
    Archives of pathology & laboratory medicine 06/2014; 138(6):809-13. · 2.78 Impact Factor
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    ABSTRACT: Background The cold agglutinin (CAGG) titer is offered at our institution to aid in diagnosing cold agglutinin disease (CAD). Our goal was to create a seasonally adjusted reference range using prospective samples and compare it to a reference range generated retrospectively.Study Design and Methods Prospective CAGG titer testing was performed on healthy blood donors. Retrospective electronic analysis was performed on patients in two groups defined by current and historical testing methods. Blood donor testing was performed in January and July to determine if seasonal variation existed. Retrospective patients with conditions associated with CAD were excluded from analysis. Additional prospective CAGG testing using reference range program volunteers was performed to verify blood donor and patient result differences.ResultsTiters from the blood donor and patient cohorts had no age association (p > 0.44). Titers from those same cohorts did not show winter/summer variation (p > 0.11). No sex association was found with titer reference ranges in the blood donor and historical patient cohort. A sex association was found with titers in the current method patient cohort (male 64 to 512 and female ≤64; p < 0.0001). Blood donor CAGG titer lower 95% reference range was not more than 4 while historical and current patient cohorts ranges were not more than 32 and not more than 64, respectively. Reference range volunteers confirmed the narrow reference range in healthy individuals when compared to patients and blood donors.Conclusion Prospective blood donor CAGG titers were lower than retrospective patient cohorts. This may be due to blood donors representing a healthier population than the patient cohorts.
    Transfusion 05/2014; 54(5). · 3.53 Impact Factor
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    ABSTRACT: The use of hematopoietic progenitor cell (HPC) transplant has risen over the past two decades. A variety of adverse events (AEs) of varying severity have been noted during HPC infusions. These AEs have been associated with several factors such as the amount of dimethyl sulfoxide and white blood cells in the HPC product. We performed a single-institution retrospective analysis to determine the effect of two different HPC infusion techniques, manual push with syringes versus infusion from bags with the aid of gravity, on the occurrence of infusion-related AEs. Infusions between December 2008 and November 2010 involving peripheral blood HPCs were reviewed. Pertinent clinical and HPC product-related information was recorded. Data were analyzed to determine the incidence of infusion-related AEs and its association with patient and product-related variables. We found 461 AEs in 645 patients during the study period. A total of 325 (50%) experienced at least one AE. Flushing was the most common type of AE followed by nausea and hypertension. The use of syringe infusion was more commonly associated with AEs (odds ratio, 1.82 [95% confidence interval, 1.32-2.50]; p = 0.002). Other independent risk factors were cryopreserved products and the amount of polymorphonuclear leukocytes in the product. To our knowledge, this is the first study examining the effect of two different infusion techniques on infusion-related AEs. Our findings suggest that the use of bags for infusion protected the patients from AEs.
    Transfusion 02/2014; · 3.53 Impact Factor
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    ABSTRACT: BACKGROUND: Variability of response to statins has been related to polymorphisms in genes involved in cholesterol homeostasis and statin metabolism, such as CYP3A4 and CYP3A5. We investigated the effects of atorvastatin on CYP3A4 and CYP3A5 mRNA expression in mononuclear cells and on CYP3A activity and their interactions with common variants. METHODS: Unrelated individuals (n=121) with hypercholesterolemia (HC) were treated with atorvastatin (10mg/day/4weeks). Ninety-two normolipidemic (NL) subjects were selected as a control group. Genotype analysis of CYP3A4*1B (rs2740574), CYP3A4*22 (rs35599367), CYP3A5*3C (rs776746), and CYP3A5*1D (rs15524) and mRNA levels in peripheral blood mononuclear cells (PBMCs) were estimated. CYP3A activity was phenotyped by the urinary cortisol to 6-beta-hydroxy-cortisol ratio. RESULTS: LDL cholesterol reduction in response to atorvastatin was positively correlated with change in CYP3A4 (R(2)=0.039, p=0.037) and CYP3A5 (R(2)=0.047, p=0.019) mRNA levels and negatively correlated with CYP3A activity (R(2)=0.071, p=0.022). CYP3A5*3C (AGT haplotype) was associated to lower basal CYP3A5 mRNA expression in HC (p<0.045), however none of the haplotype groups impacted treatment. CONCLUSION: It is likely that cholesterolemia status changes promoted by atorvastatin play a role in regulating CYP3A4 and CYP3A5 mRNA expression in PBMCs, as well as CYP3A activity. CYP3A5*3C (AGT haplotype) also contributes for the variability of CYP3A5 mRNA levels in PBMCs.
    Clinica chimica acta; international journal of clinical chemistry 03/2013; · 2.54 Impact Factor
  • Immunohematology / American Red Cross 01/2013; 29(3):101-4.
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    ABSTRACT: Late-night salivary cortisol (LNSC) measurements have been increasingly used by physicians as an initial diagnostic test for evaluation of patients with clinical suspicion of Cushing's syndrome (CS). Published studies include various numbers of cases, controls and importantly, various assay methods (vast majority various immunoassays), as well as various methods to generate cut-points. The retrospective study evaluated the diagnostic utility of LNSC measurements in 249 patients evaluated for possibility of CS because of various clinical conditions using liquid chromatography/tandem mass spectrometry method (LC-MS/MS). CS was confirmed in 47 patients (18·9%) and excluded in 202 (81·1%) patients at the time of analysis. Late-night salivary cortisol was abnormal or >2·8 nmol/l in 35 of 47 patients with CS; sensitivity of 74·5% and elevated in 20 of 202 patients who were found not to have CS; specificity 90·1%. Using receiver-operator characteristic statistics for calculation of the most optimal sensitivity and specificity, the cut-off based on this data was LNSC > 2·1 nmol/l with sensitivity of 83·0% and specificity of 84·2%. Analysis of data at one referral institution showed somewhat limited sensitivity of LNSC for diagnosis of CS using current reference ranges.
    Clinical Endocrinology 09/2011; 76(4):467-72. · 3.40 Impact Factor
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    ABSTRACT: To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort. Cumulative percentiles of amino acids and acylcarnitines in dried blood spots of approximately 25–30 million normal newborns and 10,742 deidentified true positive cases are compared to assign clinical significance, which is achieved when the median of a disorder range is, and usually markedly outside, either the 99th or the 1st percentile of the normal population. The cutoff target ranges of analytes and ratios are then defined as the interval between selected percentiles of the two populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity taking all available factors into consideration. As of December 1, 2010, 130 sites in 45 countries have uploaded a total of 25,114 percentile data points, 565,232 analyte results of true positive cases with 64 conditions, and 5,341 cutoff values. The average rate of submission of true positive cases between December 1, 2008, and December 1, 2010, was 5.1 cases/day. This cumulative evidence generated 91 high and 23 low cutoff target ranges. The overall proportion of cutoff values within the respective target range was 42% (2,269/5,341). An unprecedented level of cooperation and collaboration has allowed the objective definition of cutoff target ranges for 114 markers to be applied to newborn screening of rare metabolic disorders.
    Genetics in medicine: official journal of the American College of Medical Genetics 02/2011; 13(3):230-54. · 3.92 Impact Factor
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    ABSTRACT: The response to beta blockers in patients with heart failure could be associated with the genotype of drug-metabolizing enzymes and/or drug targets. The purpose of the present study was to determine whether specific genetic polymorphisms in ADRB1 (encoding the beta1-adrenergic receptor), CYP2D6, and UGT1A1 correlated with dose of, or response to, metoprolol or carvedilol treatment in patients with heart failure. A cohort of patients with heart failure (n = 93), characterized as responders or nonresponders to metoprolol (n = 19) or carvedilol (n = 74) therapy, was retrospectively identified. Individual genotyping was performed for a panel of polymorphisms in the ADRB1, CYP2D6, and UGT1A1 genes. Univariate and multivariate analyses were performed to compare the genotype to the metoprolol or carvedilol response status and dose. A nonresponse was identified in 10 of 19 patients taking metoprolol and 32 of 74 patients taking carvedilol. None of the polymorphisms in ADRB1, CYP2D6, and UGT1A1 were associated with a response or nonresponse. However, a significant relation between the carvedilol (but not metoprolol) dose and the ADRB1 and CYP2D6 genotype was observed. Patients homozygous for the ADRB1 389Gly variant or who were CYP2D6 poor metabolizers achieved a significantly higher dose of carvedilol (p = 0.01 and p = 0.02, respectively). In conclusion, polymorphisms in ADRB1, CYP2D6, and UGT1A1 were not associated with a response to metoprolol or carvedilol therapy in our cohort of patients with heart failure. The ADRB1 and CYP2D6 genotype, alone and in haplotype, were significantly associated with the dose of carvedilol.
    The American journal of cardiology 08/2010; 106(3):402-8. · 3.58 Impact Factor
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    ABSTRACT: Our institution has reported on delayed hemolytic transfusion reaction (DHTR) and delayed serologic transfusion reaction (DSTR) incidence changes. From January 1993 to June 2003, a polyethylene glycol (PEG) tube-based technique was used for red blood cell (RBC) antibody screen. In June 2003, a gel microcolumn technique was implemented. Impact of this on antibody detection and DHTR and DSTR incidence was investigated. Positive antibody screen frequency and antibody specificity from January 2002 to March 2003 and July 2003 to September 2004 were compared. Overall incidence of DHTR and DSTR as well as the number and identity of the RBC antibodies implicated from August 1999 through June 2003 (PEG) and July 2003 through July 2007 (gel) were compared. The mean length of hospital stay (LOS) and number of RBC units transfused per patient were compared. Equivalent numbers of antibody screens were performed with equivalent numbers of positive screens. Significant differences were not seen in the detection of clinically significant antibodies but significantly fewer clinically insignificant antibodies were detected with gel. Ninety-six DHTRs and DSTRs were diagnosed. The LOS and number of transfused RBC units were not statistically different. A significantly higher incidence of DHTRs and DSTRs was seen with PEG compared to the gel. The gel microcolumn method is similar to the PEG in detecting clinically significant antibodies but detects fewer clinically insignificant antibodies. The implementation of gel resulted in a lower incidence of DHTRs and DSTRs compared to PEG.
    Transfusion 03/2010; 50(7):1444-52. · 3.53 Impact Factor
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    ABSTRACT: This descriptive population study of 307 public high school students, ages 15 to 17 years, was performed to establish reference ranges for orthostatic changes in heart rate and blood pressure in adolescents, and to identify influential variables. Noninvasive measurements of blood pressure and heart rate were obtained. Reference ranges for orthostatic heart rate change in this population at 2 minutes were -2 to +41 beats per minute and at 5 minutes were -1 to +48 beats per minute. Orthostatic blood pressure changes were within the adult range for 98% of adolescents tested. One-third of participants experienced orthostatic symptoms during testing. In conclusion, this study shows that orthostatic symptoms and large orthostatic heart rate changes occur in adolescents. This suggests that the current orthostatic heart rate criterion aiding the diagnosis of adult orthostatic intolerance syndromes is likely not appropriate for adolescents and should be reevaluated.
    Journal of child neurology 03/2010; 25(10):1210-5. · 1.59 Impact Factor
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    ABSTRACT: Patients with ulcerative colitis (UC) are at increased risk for developing colorectal cancer (CRC). Surveillance in this at-risk population remains challenging. We assessed the methylation status of genes in the non-neoplastic mucosa of UC-CRC patients and controls to identify potential biomarkers of CRC. We evaluated the methylation status of 10 genes (p16, p14, runt-related transcript factor-3 (RUNX3), cyclooxygenase-2 (COX-2), E-cadherin, methylated-in-tumor-1 (MINT1), MINT31, HPP1, estrogen receptor, SLC5A8) in UC-CRC tumors and non-neoplastic sections from both UC-CRC cases and UC controls (n=114 for each) using methylation-specific PCR. Amplification was successful for 96 UC controls, 83 tumors, and 66 non-adjacent, non-neoplastic samples. The prevalence of methylation was significantly greater in UC-CRC tumors for p16, RUNX3, MINT1, MINT31, and HPP1. Methylation of COX-2 and E-cadherin was greater in UC controls than in tumors. Univariate testing of these genes using non-adjacent, non-neoplastic sections from UC-CRC cases indicated that associations between p16, RUNX3, MINT1, MINT31, E-cadherin, and COX-2 and UC-CRC remained significant. In multivariable analysis of the six genes, only RUNX3, MINT1, and COX-2 remained significantly associated with the UC-CRC cases (odds ratio=12.6, 9.0, and 0.2, respectively). The results remained unaffected by the presence of PSC or severity of inflammation. Logistic regression modeling with the three genes showed interactions that increased the odds ratio for each gene. RUNX3, MINT1, and COX-2 are potential biomarkers for detecting the presence of CRC in patients with UC. These genes should be evaluated as biomarkers for colorectal dysplasia.
    The American Journal of Gastroenterology 02/2010; 105(7):1610-9. · 7.55 Impact Factor
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    ABSTRACT: Metaplastic breast carcinoma (MBC) is a rare subtype of breast cancer characterized by coexistence of carcinomatous and sarcomatous components. Snail is a nuclear transcription factor incriminated in the transition of epithelial to mesenchymal differentiation of breast cancer. Aberrant Snail expression results in lost expression of the cell adhesion molecule E-cadherin, an event associated with changes in epithelial architecture and invasive growth. We aimed to identify the utility of Snail, and of traditional immunohistochemical markers, in accurate MBC classification and to evaluate clinicopathologic characteristics and outcome.We retrospectively reviewed 34 MBC cases from January 1997 to September 2007. The control group contained 26 spindle cell lesions. Immunohistochemistry used Snail, p63, epidermal growth factor receptor (EGFR), OSCAR, and wide spectrum cytokeratin (WS-KER). Negative was a score less than 1%. We found that Snail and EGFR are sensitive (100%) markers with low specificity (3.8% and 19.2%) for detecting MBC. p63 and WS-KER are specific (100%), with moderate sensitivity (67.6% and 76.5%); OSCAR is sensitive (85.3%) and specific (92.3%). A combination of any 2 of the p63, OSCAR, and WS-KER markers increased sensitivity and specificity. MBCs tended to be high-grade (77%), triple negative (negative for estrogen receptor, progesterone receptor, and HER2) [27/33; 81.8%], and carcinomas with low incidence of axillary lymph node involvement (15%), and decreased disease-free [71% (95%CI: 54%, 94%) at 3 yrs.) and overall survival. A combination of p63, OSCAR and WS-KER are useful in its work-up. On the other hand, Snail is neither a diagnostic nor a prognostic marker for MBC.
    Diagnostic Pathology 01/2010; 5:76. · 1.85 Impact Factor
  • Gastroenterology 01/2010; 138(5). · 12.82 Impact Factor
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    ABSTRACT: Patient involvement in the choice of antihyperglycemic agents could improve adherence and optimize glycemic control in patients with type 2 diabetes mellitus. We conducted a pilot, cluster randomized trial of Diabetes Medication Choice, a decision aid that describes 5 antihyperglycemic drugs, their treatment burden (adverse effects, administration, and self-monitoring demands), and impact on hemoglobin A(1c) (HbA(1c)) levels. Twenty-one clinicians were randomized to use the decision aid during the clinical encounter and 19 to dispense usual care and an educational pamphlet. We used surveys and video analysis to assess postvisit decisional outcomes, and medical and pharmacy records to assess 6-month medication adherence and HbA(1c) levels. Compared with usual care patients (n = 37), patients receiving the decision aid (n = 48) found the tool more helpful (clustered-adjusted mean difference [AMD] in a 7-point scale, 0.38; 95% confidence interval [CI], 0.04-0.72); had improved knowledge (AMD, 1.10 of 10 questions; 95% CI, 0.11-2.09); and had more involvement in making decisions about diabetes medications (AMD, 21.8 of 100; 95% CI, 13.0-30.5). At 6-month follow-up, both groups had nearly perfect medication use (median, 100% of days covered), with better adherence (AMD, 9% more days covered; 95% CI, 4%-14%) and persistence (AMD, 12 more days covered; 95% CI, 3-21 days) in the usual care group, and no significant impact on HbA(1c) levels (AMD, 0.01; 95% CI, -0.49 to 0.50). An innovative decision aid effectively involved patients with type 2 diabetes mellitus in decisions about their medications but did not improve adherence or HbA(1c) levels. Trial Registration clinicaltrials.gov Identifier: NCT00388050.
    Archives of internal medicine 09/2009; 169(17):1560-8. · 11.46 Impact Factor
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    ABSTRACT: Natriuretic peptide concentrations in adults require age- and sex-specific reference intervals for optimal interpretation. Females have higher natriuretic peptide concentrations, and hypotheses suggest that estrogen may be responsible. This study sought to determine the influence of hormone modulation on N-terminal probrain natriuretic peptide (NT-proBNP) by using a pediatric cohort. Children/adolescents typically have rapid hormone changes during puberty, making them an ideal group to study. We selected 759 specimens (303 male, 456 female; ages 2 months to 18 years, mean 13 years) obtained from the Mayo Clinic Pediatric Residual Specimen Bank. We measured NT-proBNP, sex hormone-binding globulin (SHBG), estradiol, and testosterone by immunoassays or LC-MS/MS and calculated free testosterone. We performed univariate and multivariate analyses to investigate the significance of NT-proBNP with each hormone. Reference values demonstrated a sex difference and sequential age differences in females. Univariate modeling of the hormones with NT-proBNP revealed an independent inverse association of NT-proBNP with testosterone, a direct association with SHBG, and no significant association with estradiol. Multivariate modeling confirmed a strong association of testosterone and SHBG with NT-proBNP. Correlation of hormones with NT-proBNP retained greater significance than either age or sex. In pediatric patients, NT-proBNP is independently associated with both testosterone and SHBG hormone concentrations. Measurements of testosterone are inversely associated with NT-proBNP, and estrogens are marginally associated with NT-proBNP in males but not females, suggesting that androgens and not estrogens modulate sex differences notable in natriuretic peptides. Children and adolescents may require an objective assessment of hormones if optimal interpretation of natriuretic peptide concentrations is desired or the concentrations are confounded. .
    Clinical Chemistry 09/2009; 55(10):1869-75. · 7.15 Impact Factor
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    ABSTRACT: Clinicians often use validated risk models to guide treatment decisions for cardiovascular risk reduction. The most common risk models for predicting cardiovascular risk are the UKPDS, Framingham, and Archimedes models. In this article, the authors propose a model to optimize the selection of patients for statin therapy of hypercholesterolemia, for patients with type 2 diabetes, using each of the risk models. For each model,they evaluate the role of age, gender, and metabolic state on the optimal start time for statins. Using clinical data from the Mayo Clinic electronic medical record, the authors construct a Markov decision process model with health states composed of cardiovascular events and metabolic factors such as total cholesterol and high-density lipoproteins. They use it to evaluate the optimal start time of statin treatment for different combinations of cardiovascular risk models and patient attributes. The authors find that treatment decisions depend on the cardiovascular risk model used and the age, gender, and metabolic state of the patient. Using the UKPDS risk model to estimate the probability of coronary heart disease and stroke events, they find that all white male patients should eventually start statin therapy; however, using Framingham and Archimedes models in place of UKPDS, they find that for male patients at lower risk, it is never optimal to initiate statins. For white female patients, the authors also find some patients for whom it is never optimal to initiate statins. Assuming that age 40 is the earliest possible start time, the authors find that the earliest optimal start times for UKPDS, Framingham, and Archimedes are 50, 46, and 40, respectively, for women. For men, the earliest optimal start times are 40, 40, and 40, respectively. In addition to age, gender, and metabolic state, the choice of cardiovascular risk model influences the apparent optimal time for starting statins in patients with diabetes.
    Medical Decision Making 06/2009; 29(3):351-67. · 2.89 Impact Factor
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    ABSTRACT: Decision aids in practice may affect patient trust in the clinician, a requirement for optimal diabetes care. We sought to determine the impact of a decision aid to help patients with diabetes decide about statins (Statin Choice) on patients' trust in the clinician. We randomized 16 diabetologists and 98 patients with type 2 diabetes referred to a subspecialty diabetes clinic to use the Statin Choice decision aid or a patient pamphlet about dyslipidaemia, and then to receive these materials from either the clinician during the visit or a researcher prior to the visit. Providers and patients were blinded to the study hypothesis. Immediately after the clinical encounter, patients completed a survey including questions on trust (range 0 to total trust = 100), knowledge, and decisional conflict. Researchers reviewed videotaped encounters and assessed patient participation (using the OPTION scale) and visit length. Overall mean trust score was 91 (median 97.2, IQR 86, 100). After adjustment for patient characteristics, results suggested greater total trust (trust = 100) with the decision aid [odds ratio (OR) 1.77, 95% CI 0.94, 3.35]. Total trust was associated with knowledge (for each additional knowledge point, OR 1.3, 95% CI 1.1, 1.6), patient participation (for each additional point in the OPTION scale, OR 1.1, 95% CI 1.1, 1.2), and decisional conflict (for every 5-point decrease in conflict, OR 1.5, 95% CI 1.2, 1.9). Total trust was not associated with visit length, which the decision aid did not significantly affect. There was no significant effect interaction across the trial factors. Preliminary evidence suggests that decision aids do not have a large negative impact on trust in the physician and may increase trust through improvements in the decision-making process.
    Health expectations: an international journal of public participation in health care and health policy 04/2009; 12(1):38-44. · 1.80 Impact Factor
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    ABSTRACT: Ancillary cytologic tests including digital image analysis (DIA) and fluorescence in situ hybridization (FISH) have been developed to improve the sensitivity of routine cytology (RC) for the diagnosis of malignancy in pancreatobiliary strictures. The goal of this study was to retrospectively compare the performance of RC, DIA, and FISH on clinical brushing specimens. Endoscopic retrograde cholangiopancreatography brushings were obtained from 498 consecutive patients with pancreatobiliary strictures and analyzed by RC, DIA, and FISH as per standard practice. RC diagnostic categories included negative, atypical, suspicious, or positive. Aneuploid/tetraploid histograms were considered positive for DIA. FISH was performed using UroVysion (Abbott Molecular, Inc, Des Plaines, IL) and classified as negative, trisomy, tetrasomy, or polysomy. The sensitivity of polysomy FISH (42.9%) was significantly higher than RC (20.1%) when equivocal RC results were considered negative (P < .001) with identical specificity (99.6%). There was a significant difference in time for diagnosis of carcinoma between FISH diagnostic categories (P < .001) and between RC diagnostic categories (P < .001). Logistic regression analysis revealed that polysomy FISH, trisomy FISH, suspicious cytology, primary sclerosing cholangitis status, and age were associated with carcinoma (P < .05). Polysomy FISH had high sensitivity without compromise to specificity. DIA was not a significant independent predictor of malignancy. Multivariable modeling using RC, FISH, age, and primary sclerosing cholangitis status can be used to estimate the probability of carcinoma for an individual patient. We recommend including FISH as a routine test where available, along with RC, in the evaluation of indeterminate pancreatobiliary strictures.
    Gastroenterology 03/2009; 136(7):2180-6. · 12.82 Impact Factor
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    ABSTRACT: Patients with ulcerative colitis are at risk for colorectal cancer (CRC). Although prior studies have shown a link between HLA genotypes and ulcerative colitis (UC) susceptibility, none have investigated HLA genotypes and UC-CRC. We therefore investigated HLA-DR/DQ alleles in UC-CRC cases and UC-controls. Furthermore, since methylation of the Class II transactivator (CIITA) gene may silence HLA expression in tumours, we correlated HLA allele frequencies with CIITA gene methylation and HLA-DR expression. Cases and controls were matched for duration/extent of ulcerative colitis, age, ethnicity and gender, but not for primary sclerosing cholangitis (PSC). DNA was extracted from archived tissue blocks from 114 UC-CRC cases and 114 UC-controls. HLA-DR/DQ genotyping was performed using sequence-specific-oligonucleotide polymerase chain reaction (SSO-PCR). CIITA methylation was determined using methylation-specific PCR. HLA-DR immunohistochemistry was done following standard protocols. UC-CRC cases were more likely than UC-controls to carry the DR17 or DR13 alleles (p<0.0001 or p = 0.02, respectively). Although CIITA methylation did not vary significantly between cases and controls, DR17 and DQ2 were associated with CIITA methylation (p = 0.04 and 0.02, respectively). UC-controls more frequently carried the DR7, DR1 or DQ5 alleles (p = 0.002, 0.05 or 0.01, respectively). After adjusting for PSC, DR17 remained significantly associated with an increased risk for UC-CRC while DR7 and DQ5 remained protective. We report a significant association between specific HLA alleles and either the risk for (DR17) or protection from (DR7, DQ5) UC-CRC. This suggests a possible genetic predisposition for increased UC-CRC risk. In addition, DQ2 and DR17 were associated with CIITA methylation.
    Gut 02/2009; 58(9):1226-33. · 10.73 Impact Factor

Publication Stats

2k Citations
289.58 Total Impact Points

Institutions

  • 1996–2014
    • Mayo Clinic - Rochester
      • • Department of Laboratory Medicine & Pathology
      • • Department of Health Science Research
      • • Department of Endocrinology, Diabetes, Metabolism and Nutrition
      • • Department of Anesthesiology
      Rochester, Minnesota, United States
  • 2001–2011
    • Mayo Foundation for Medical Education and Research
      • • Division of Endocrinology, Diabetes, Metabolism, and Nutrition
      • • Division of Gastroenterology and Hepatology
      • • Department of Health Sciences Research
      • • Department of Medicine
      • • Department of Anesthesiology
      Jacksonville, FL, United States
  • 2010
    • The University of Chicago Medical Center
      Chicago, Illinois, United States
  • 2009
    • North Carolina State University
      Raleigh, North Carolina, United States
    • University of California, Irvine
      • Department of Planning, Policy and Design
      Irvine, CA, United States