Ductal carcinoma in situ of the breast (DCIS) with heterogeneity of nuclear grade: prognostic effects of quantitative nuclear assessment.

BACKGROUND: Previously, 50% of patients with breast ductal carcinoma in situ (DCIS) had more than one nuclear grade, and neither worst nor predominant nuclear grade was significantly associated with development of invasive carcinoma. Here, we used image analysis in addition to histologic evaluation to determine if quantification of nuclear features could provide additional prognostic information and hence impact prognostic assessments. METHODS: Nuclear image features were extracted from about 200 nuclei of each of 80 patients with DCIS who underwent lumpectomy alone, and received no adjuvant systemic therapy. Nuclear images were obtained from 20 representative nuclei per duct, from each of a group of 5 ducts, in two separate fields, for 10 ducts. Reproducibility of image analysis features was determined, as was the ability of features to discriminate between nuclear grades. Patient information was available about clinical factors (age and method of DCIS detection), pathologic factors (DCIS size, nuclear grade, margin size, and amount of parenchymal involvement), and 39 image features (morphology, densitometry, and texture). The prognostic effects of these factors and features on the development of invasive breast cancer were examined with Cox step-wise multivariate regression. RESULTS: Duplicate measurements were similar for 89.7% to 97.4% of assessed image features. For the pooled assessment with approximately 200 nuclei per patient, a discriminant function with one densitometric and two texture features was significantly (p < 0.001) associated with nuclear grading, and provided 78.8% correct jackknifed classification of a patient's nuclear grade. In multivariate assessments, image analysis nuclear features had significant prognostic associations (p

Identifying medication misadventures: poor agreement among medical record, physician, nurse, and patient reports.

STUDY OBJECTIVE: To analyze and compare four different methods of detecting medication misadventures in order to determine the optimal system for reporting clinically observed medication misadventures. DESIGN: Prospective cohort study. SETTING: Forty-eight-bed general internal medicine inpatient ward at a large academic teaching hospital with a decentralized pharmacy system. PATIENTS: One hundred twenty-six patients (54% male, mean age 54 yrs) with 133 consecutive admissions to the ward (mean length of stay 7.8 days) over an 8-week period from December 2001-February 2002. INTERVENTION: Medication misadventures were detected by four methods: house staff (resident physicians) report during their morning conference, nursing report during shift change, patient report at the discharge interview, and standardized medical record review. All methods of reporting medication misadventures were compared with the hospital's existing electronic medication misadventure reporting system. MEASUREMENTS AND MAIN RESULTS: Overall, 63 patients (47% of 133 admissions) experienced at least one medication misadventure. Thirty-seven adverse drug events (ADEs) and 69 medication errors were observed over 1035 patient bed-days. Little overlap was noted among the four intervention methods, with nearly 80% of all 106 events detected by only a single method (medical record review 51% [54 events], patient interview 11% [12], house-staff report 9% [10], nurse report 8% [9]). Of the 37 ADEs, 6 (16%) were due to medication errors and 10 (27%) were preventable. Of five life-threatening ADEs, all were preventable, and all were reported in the medical record and the electronic reporting system; however, only two were reported by a nurse, two by a resident physician, and one by a patient. CONCLUSION: Little overlap was noted among the individual medication misadventure reporting methods, suggesting the need to use multiple complementary methods to identify medication misadventures in hospitalized patients. These findings have important implications for development of surveillance systems, design of prevention initiatives, and future medication safety research.

Heterogeneity Between Ducts of the Same Nuclear Grade Involved by Duct Carcinoma In Situ (DCIS) of the Breast.

PURPOSE: Nuclear grade of breast DCIS is considered during patient management decision-making although it may have only a modest prognostic association with therapeutic outcome. We hypothesized that visual inspection may miss substantive differences in nuclei classified as having the same nuclear grade. To test this hypothesis, we measured subvisual nuclear features by quantitative image cytometry for nuclei with the same grade, and tested for statistical differences in these features. EXPERIMENTAL DESIGN AND STATISTICAL ANALYSIS: Thirty-nine nuclear digital image features of about 100 nuclei were measured in digital images of H&E stained slides of 81 breast biopsy specimens. One field with at least 5 ducts was evaluated for each patient. We compared features of nuclei with the same grade in multiple ducts of the same patient with ANOVA (or Welch test), and compared features of nuclei with the same grade in two ducts of different patients using 2-sided t-tests (P ≤ 0.05). Also, we compared image features for nuclei in patients with single grade to those with the same grade in patients with multiple grades using t-tests. RESULTS: Statistically significant differences were detected in nuclear features between ducts with the same nuclear grade, both in different ducts of the same patient, and between ducts in different patients with DCIS of more than one grade. CONCLUSION: Nuclei in ducts visually described as having the same nuclear grade had significantly different subvisual digital image features. These subvisual differences may be considered additional manifestations of heterogeneity over and above differences that can be observed microscopically. This heterogeneity may explain the inconsistency of nuclear grading as a prognostic factor.

Effect of quantitative nuclear image features on recurrence of Ductal Carcinoma In Situ (DCIS) of the breast.

BACKGROUND: Nuclear grade has been associated with breast DCIS recurrence and progression to invasive carcinoma; however, our previous study of a cohort of patients with breast DCIS did not find such an association with outcome. Fifty percent of patients had heterogeneous DCIS with more than one nuclear grade. The aim of the current study was to investigate the effect of quantitative nuclear features assessed with digital image analysis on ipsilateral DCIS recurrence. METHODS: Hematoxylin and eosin stained slides for a cohort of 80 patients with primary breast DCIS were reviewed and two fields with representative grade (or grades) were identified by a Pathologist and simultaneously used for acquisition of digital images for each field. Van Nuys worst nuclear grade was assigned, as was predominant grade, and heterogeneous grading when present. Patients were grouped by heterogeneity of their nuclear grade: Group A: nuclear grade 1 only, nuclear grades 1 and 2, or nuclear grade 2 only (32 patients), Group B: nuclear grades 1, 2 and 3, or nuclear grades 2 and 3 (31 patients), Group 3: nuclear grade 3 only (17 patients). Nuclear fine structure was assessed by software which captured thirty-nine nuclear feature values describing nuclear morphometry, densitometry, and texture. Step-wise forward Cox regressions were performed with previous clinical and pathologic factors, and the new image analysis features. RESULTS: Duplicate measurements were similar for 89.7% to 97.4% of assessed image features. The rate of correct classification of nuclear grading with digital image analysis features was similar in the two fields, and pooled assessment across both fields. In the pooled assessment, a discriminant function with one nuclear morphometric and one texture feature was significantly (p = 0.001) associated with nuclear grading, and provided correct jackknifed classification of a patient's nuclear grade for Group A (78.1%), Group B (48.4%), and Group C (70.6%). The factors significantly associated with DCIS recurrence were those previously found, type of initial presentation (p = 0.03) and amount of parenchymal involvement (p = 0.05), along with the morphometry image feature of ellipticity (p = 0.04). CONCLUSION: Analysis of nuclear features measured by image cytometry may contribute to the classification and prognosis of breast DCIS patients with more than one nuclear grade.

Is there a July phenomenon? The effect of July admission on intensive care mortality and length of stay in teaching hospitals.

BACKGROUND: It has been suggested that inexperience of new housestaff early in an academic year may worsen patient outcomes. Yet, few studies have evaluated the "July Phenomenon," and no studies have investigated its effect in intensive care patients, a group that may be particularly susceptible to deficiencies in management stemming from housestaff inexperience. OBJECTIVE: Compare hospital mortality and length of stay (LOS) in intensive care unit (ICU) admissions from July to September to admissions during other months, and compare that relationship in teaching and nonteaching hospitals, and in surgical and nonsurgical patients. DESIGN, SETTING, AND PATIENTS: Retrospective cohort analysis of 156,136 consecutive eligible patients admitted to 38 ICUs in 28 hospitals in Northeast Ohio from 1991 to 1997. RESULTS: Adjusting for admission severity of illness using the APACHE III methodology, the odds of death was similar for admissions from July through September, relative to the mean for all months, in major (odds ratio [OR], 0.96; 95% confidence interval [95% CI], 0.91 to 1.02; P =.18), minor (OR, 1.02; 95% CI, 0.93 to 1.10; P =.66), and nonteaching hospitals (OR, 0.96; 95% CI, 0.91 to 1.01; P =.09). The adjusted difference in ICU LOS was similar for admissions from July through September in major (0.3%; 95% CI, -0.7% to 1.2%; P =.61) and minor (0.2%; 95% CI, -0.9% to 1.4%; P =.69) teaching hospitals, but was somewhat shorter in nonteaching hospitals (-0.8%; 95% CI, -1.4% to -0.1%; P =.03). Results were similar when individual months and academic years were examined separately, and in stratified analyses of surgical and nonsurgical patients. CONCLUSIONS: We found no evidence to support the existence of a July phenomenon in ICU patients. Future studies should examine organizational factors that allow hospitals and residency programs to compensate for inexperience of new housestaff early in the academic year.