Michelle Moghadassi

Ultrasonography versus Computed Tomography for Suspected Nephrolithiasis

BACKGROUND There is a lack of consensus about whether the initial imaging method for patients with suspected nephrolithiasis should be computed tomography (CT) or ultrasonography. METHODS In this multicenter, pragmatic, comparative effectiveness trial, we randomly assigned patients 18 to 76 years of age who presented to the emergency department with suspected nephrolithiasis to undergo initial diagnostic ultrasonography performed by an emergency physician (point-of-care ultrasonography), ultrasonography performed by a radiologist (radiology ultrasonography), or abdominal CT. Subsequent management, including additional imaging, was at the discretion of the physician. We compared the three groups with respect to the 30-day incidence of high-risk diagnoses with complications that could be related to missed or delayed diagnosis and the 6-month cumulative radiation exposure. Secondary outcomes were serious adverse events, related serious adverse events (deemed attributable to study participation), pain (assessed on an 11-point visual-analogue scale, with higher scores indicating more severe pain), return emergency department visits, hospitalizations, and diagnostic accuracy. RESULTS A total of 2759 patients underwent randomization: 908 to point-of-care ultrasonography, 893 to radiology ultrasonography, and 958 to CT. The incidence of high-risk diagnoses with complications in the first 30 days was low (0.4%) and did not vary according to imaging method. The mean 6-month cumulative radiation exposure was significantly lower in the ultrasonography groups than in the CT group (P<0.001). Serious adverse events occurred in 12.4% of the patients assigned to point-of-care ultrasonography, 10.8% of those assigned to radiology ultrasonography, and 11.2% of those assigned to CT (P=0.50). Related adverse events were infrequent (incidence, 0.4%) and similar across groups. By 7 days, the average pain score was 2.0 in each group (P=0.84). Return emergency department visits, hospitalizations, and diagnostic accuracy did not differ significantly among the groups. CONCLUSIONS Initial ultrasonography was associated with lower cumulative radiation exposure than initial CT, without significant differences in high-risk diagnoses with complications, serious adverse events, pain scores, return emergency department visits, or hospitalizations. (Funded by the Agency for Healthcare Research and Quality.).

Reduced Immunoglobulin E and Allergy among Adults with Glioma Compared with Controls

We and others have reported previously that adults with glioma are 1.5- to 4-fold less likely than controls to report a variety of allergic conditions. The consistent nature of this relationship calls for a biological explanation so that preventative or therapeutic modalities can be explored. We enrolled 403 newly diagnosed adult glioma cases in the San Francisco Bay Area over a 3-year period using a population-based cancer registry and 402 age/gender/ethnicity frequency-matched controls identified via random digit dialing. We assessed total, food-specific, and respiratory-specific IgE in available case (n = 228) and control (n = 289) serum samples. IgE levels were associated with gender, age, smoking status, and ethnicity among cases and/or controls. Among the cases, IgE levels were not associated with aspects of glioma therapy including radiation, chemotherapy, or tumor resection. Total IgE levels were lower in cases than controls: age/gender/ethnicity/education/smoking-adjusted odds ratio (OR) for elevated versus normal total IgE was 0.37 [95% confidence interval (CI), 0.22–0.64]. For the food panel, OR was 0.12 (95% CI, 0.04–0.41). For the respiratory panel, OR was 0.76 (95% CI, 0.52–1.1). Among respiratory allergies, late age of onset (>12 years) but not IgE levels defined a group with strong associations with risk (OR, 0.50; 95% CI, 0.33–0.75). These results corroborate and strengthen our findings of an inverse association between allergic reactions and glioma by showing a relationship with a biomarker for allergy and cancer for the first time. Furthermore, the results indicate a complex relationship between allergic disease and glioma risk that varies by allergen and allergic pathology.

Allergy-Related Polymorphisms Influence Glioma Status and Serum IgE Levels

Previous studies have shown that glioma patients report allergies less frequently than controls, harbor lower atopy-associated IgE levels, and harbor different frequencies of polymorphisms in the IL13 and IL4 pathways than controls. We sought to confirm this latter result and extend the analysis to IgE levels. Glioma patients (n = 456) and controls (n = 541) were genotyped for genetic variants in IL4, IL4R, and IL13 and tested for total IgE levels (n = 248 controls and 289 cases). Among Whites, IL4 and IL4R polymorphisms and haplotypes were neither significantly associated with IgE levels in controls nor associated with glioma status. IL13 R110G and C-1112T were associated with increased IgE levels in controls (P < 0.001 and P = 0.04, respectively), and IL13 C-1112T was inversely associated with case-control status (P = 0.05, test for trend in dose model). An IL4R haplotype was borderline associated with increased risk in case-control analysis [odds ratio (OR), 1.5; 95% confidence interval (95% CI), 1.0-2.3]. In addition, a rare haplotype for IL4 was associated with decreased risk (OR, 0.23; 95% CI, 0.07-0.83), and a common haplotype in IL13 was associated with decreased risk (OR, 0.73; 95% CI, 0.53-1.00). Our data provide evidence for a role of IL13 polymorphisms on IgE levels and a role for IL4, IL4R, and IL13 haplotypes on case-control status. We did not find any evidence that the interleukin (IL) polymorphisms exerted their effect on glioma risk via their effects on IgE levels. Further exploration of immune susceptibility factors, including genetics, in glioma etiology is advisable. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1229–35)

Radiation doses in consecutive ct examinations from five university of California medical centers 1

PURPOSE To summarize data on computed tomographic (CT) radiation doses collected from consecutive CT examinations performed at 12 facilities that can contribute to the creation of reference levels. MATERIALS AND METHODS The study was approved by the institutional review boards of the collaborating institutions and was compliant with HIPAA. Radiation dose metrics were prospectively and electronically collected from 199 656 consecutive CT examinations in 83 181 adults and 3871 consecutive CT examinations in 2609 children at the five University of California medical centers during 2013. The median volume CT dose index (CTDIvol), dose-length product (DLP), and effective dose, along with the interquartile range (IQR), were calculated separately for adults and children and stratified according to anatomic region. Distributions for DLP and effective dose are reported for single-phase examinations, multiphase examinations, and all examinations. RESULTS For adults, the median CTDIvol was 50 mGy (IQR, 37-62 mGy) for the head, 12 mGy (IQR, 7-17 mGy) for the chest, and 12 mGy (IQR, 8-17 mGy) for the abdomen. The median DLPs for single-phase, multiphase, and all examinations, respectively, were as follows: head, 880 mGy · cm (IQR, 640-1120 mGy · cm), 1550 mGy · cm (IQR, 1150-2130 mGy · cm), and 960 mGy · cm (IQR, 690-1300 mGy · cm); chest, 420 mGy · cm (IQR, 260-610 mGy · cm), 880 mGy · cm (IQR, 570-1430 mGy · cm), and 550 mGy · cm (IQR 320-830 mGy · cm); and abdomen, 580 mGy · cm (IQR, 360-860 mGy · cm), 1220 mGy · cm (IQR, 850-1790 mGy · cm), and 960 mGy · cm (IQR, 600-1460 mGy · cm). Median effective doses for single-phase, multiphase, and all examinations, respectively, were as follows: head, 2 mSv (IQR, 1-3 mSv), 4 mSv (IQR, 3-8 mSv), and 2 mSv (IQR, 2-3 mSv); chest, 9 mSv (IQR, 5-13 mSv), 18 mSv (IQR, 12-29 mSv), and 11 mSv (IQR, 6-18 mSv); and abdomen, 10 mSv (IQR, 6-16 mSv), 22 mSv (IQR, 15-32 mSv), and 17 mSv (IQR, 11-26 mSv). In general, values for children were approximately 50% those for adults in the head and 25% those for adults in the chest and abdomen. CONCLUSION These summary dose data provide a starting point for institutional evaluation of CT radiation doses.

The C3435T Polymorphism of MDR1 and Susceptibility to Adult Glioma

Introduction: The multidrug resistance-1 (MDR1) gene encodes a pump that prevents potentially carcinogenic substances from crossing the blood-brain barrier. We compare adult glioma cases and controls for the C3435T polymorphism that has been associated with reduced MDR1 expression. Methods: Adult glioma in the San Francisco Bay area and population-based controls were identified between 1991–1994 and 1997–1999. Genotyped cases (n = 458) and controls (n = 528) were compared using logistic regression controlling for age, gender and ethnicity, with later stratification by ethnicity, gender and histology. Results: With CC as the referent, the TT genotype was nonsignificantly less frequent among cases compared to controls (OR, 0.87; 95% CI: 0.6, 1.2). After stratification, only male glioblastoma was associated with TT genotype (OR, 0.51; 95% CI: 0.3, 1.0). Conclusions: Although the C3435T polymorphism does not appear to be associated with other types of glioma, we cannot rule out that this MDR1 polymorphism may be associated with glioblastoma among men.

Epithelial cells in nipple aspirate fluid and subsequent breast cancer risk: A historic prospective study

BackgroundPast studies have shown that women with abnormal cytology or epithelial cells in nipple aspirate fluid (NAF) have an increased relative risk (RR) of breast cancer when compared to women from whom NAF was attempted but not obtained (non-yielders). This study analyzed NAF results from a group of women seen in a breast clinic between 1970–1991 (N = 2480). Our analysis presented here is an aggregate of two sub-groups: women with questionnaire data (n = 712) and those with NAF visits beginning in 1988 (n = 238), the year in which cancer case information was uniformly collected in California.MethodsCytological classification was determined for a group of 946 women using the most abnormal epithelial cytology observed in fluid specimens. Breast cancer incidence and mortality status was determined through June 2006 using data from the California Cancer Registry, California Vital Statistics and self-report. We estimated odd ratios (ORs) for breast cancer using logistic regression analysis, adjusting for age. We analyzed breast cancer risk related to abnormality of NAF cytology using non-yielders as the referent group and breast cancer risk related to the presence or absence of epithelial cells in NAF, using non-yielders/fluid without epithelial cells as the referent group.ResultsOverall, 10% (93) of the 946 women developed breast cancer during the follow-up period. Age-adjusted ORs and 95% confidence intervals (C.I.) compared to non-yielders were 1.4 (0.3 to 6.4), 1.7 (0.9 to 3.5), and 2.0 (1.1 to 3.6) for women with fluid without epithelial cells, normal epithelial cells and hyperplasia/atypia, respectively. Comparing the presence or absence of epithelial cells in NAF, women with epithelial cells present in NAF were more likely to develop breast cancer than non-yielders or women with fluid without epithelial cells (RR = 1.9, 1.2 to 3.1).ConclusionThese results support previous findings that 1) women with abnormal epithelial cells in NAF have an increased risk of breast cancer when compared to non-yielders or women with normal epithelial cells in NAF and 2) women with epithelial cells present in NAF have an increased risk of breast cancer when compared to non-yielders or women who had NAF without epithelial cells present.

Nonsynonymous Coding Single-Nucleotide Polymorphisms Spanning the Genome in Relation to Glioblastoma Survival and Age at Diagnosis

Purpose: Our aim was to discover possible inherited factors associated with glioblastoma age at diagnosis and survival. Although new genotyping technologies allow greatly expanded exploration of such factors, they pose many challenges. Experimental Design: In this pilot study, we (a) genotyped 112 newly diagnosed glioblastoma patients ascertained through a population-based study (group 1) with the ParAllele assay panel of ∼10,000 nonsynonymous coding single-nucleotide polymorphisms (SNP), (b) used several statistical and bioinformatic techniques to identify 17 SNPs potentially related to either glioblastoma age at diagnosis or survival, and (c) genotyped 16 of these SNPs using conventional PCR methods in an independent group of 195 glioblastoma patients (group 2). Results: In group 2, only one of the 16 SNPs, rs8057643 (located on 16p13.2), was significantly associated with glioblastoma age at diagnosis (nominal P = 0.0017; Bonferroni corrected P = 0.054). Median ages at diagnosis for those with 0, 1, or 2 T alleles were 66, 57, and 59 years in group 1 and 64, 57, and 55 years in group 2 (combined P = 0.001). Furthermore, Cox regression analyses of time to death with number of T alleles adjusted for gender and patient group yielded a hazard ratio of 0.82 (95% confidence interval, 0.68-0.98; P = 0.03). Conclusions: Although limited by a relatively small sample size, this pilot study, using well-characterized, unambiguous disease characteristics, illustrates the necessity of independent replication owing to the likelihood of false positives. Several other challenges are discussed, including attempts to incorporate information on the potential functional importance of SNPs in genome-disease association studies.

External Validation of the STONE Score, a Clinical Prediction Rule for Ureteral Stone: An Observational Multi-institutional Study

Study objective The STONE score is a clinical decision rule that classifies patients with suspected nephrolithiasis into low-, moderate-, and high-score groups, with corresponding probabilities of ureteral stone. We evaluate the STONE score in a multi-institutional cohort compared with physician gestalt and hypothesize that it has a sufficiently high specificity to allow clinicians to defer computed tomography (CT) scan in patients with suspected nephrolithiasis. Methods We assessed the STONE score with data from a randomized trial for participants with suspected nephrolithiasis who enrolled at 9 emergency departments between October 2011 and February 2013. In accordance with STONE predictors, we categorized participants into low-, moderate-, or high-score groups. We determined the performance of the STONE score and physician gestalt for ureteral stone. Results Eight hundred forty-five participants were included for analysis; 331 (39%) had a ureteral stone. The global performance of the STONE score was superior to physician gestalt (area under the receiver operating characteristic curve=0.78 [95% confidence interval {CI} 0.74 to 0.81] versus 0.68 [95% CI 0.64 to 0.71]). The prevalence of ureteral stone on CT scan ranged from 14% (95% CI 9% to 19%) to 73% (95% CI 67% to 78%) in the low-, moderate-, and high-score groups. The sensitivity and specificity of a high score were 53% (95% CI 48% to 59%) and 87% (95% CI 84% to 90%), respectively. Conclusion The STONE score can successfully aggregate patients into low-, medium-, and high-risk groups and predicts ureteral stone with a higher specificity than physician gestalt. However, in its present form, the STONE score lacks sufficient accuracy to allow clinicians to defer CT scan for suspected ureteral stone.

Cost Analysis of the STONE Randomized Trial: Can Health Care Costs be Reduced One Test at a Time?

Background:Decreasing the use of high-cost tests may reduce health care costs. Objective:To compare costs of care for patients presenting to the emergency department (ED) with suspected kidney stones randomized to 1 of 3 initial imaging tests. Research Design:Patients were randomized to point-of-care ultrasound (POC US, least costly), radiology ultrasound (RAD US), or computed tomography (CT, most costly). Subsequent testing and treatment were the choice of the treating physician. Subjects:A total of 2759 patients at 15 EDs were randomized to POC US (n=908), RAD US, (n=893), or CT (n=958). Mean age was 40.4 years; 51.8% were male. Measures:All medical care documented in the trial database in the 7 days following enrollment was abstracted and coded to estimate costs using national average 2012 Medicare reimbursements. Costs for initial ED care and total 7-day costs were compared using nonparametric bootstrap to account for clustering of patients within medical centers. Results:Initial ED visit costs were modestly lower for patients assigned to RAD US:

Computed Tomography Radiation Dose in Patients With Suspected Urolithiasis

423 (