Faculty Bibliography

Cheville AL, Basford JR, Troxel AB, Kornblith AB. Performance of common clinician- and self-report measures in assessing the function of community-dwelling people with metastatic breast cancer. OBJECTIVE: To characterize the performance of common clinician- and self-report measures of function in assessing community-dwelling people with metastatic breast cancer. DESIGN: Cross-sectional study. SETTING: A tertiary medical center outpatient cancer clinic. PARTICIPANTS: A consecutive sample of community-dwelling patients (N=163) with stage IV breast cancer. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Medical Outcomes Study 36-Item Short-Form Physical Functioning (PF-10) and Role Physical subscales; the Older Americans Resource Study (OARS) activities of daily living (ADL) and instrumental ADL subscales; Karnofsky Performance Scale (KPS); and the FIM Total and FIM Mobility scores. RESULTS: With the exception of the PF-10 and Role Physical subscales, which demonstrated floor effects, ceiling effects were detected in all the measures and were particularly persistent in the OARS ADL subscale. Instrument and item score distributions varied markedly across KPS-defined subgroups with FIM Mobility, FIM Total, and OARS subscale score distributions deviating least from the normal in the lowest performing (KPS 40-50) participants. Correlations between self-reported (Role Physical subscales, PF-10, OARS ADL subscales) and the clinician-rated (KPS and FIM scales) scales were moderate to high (r=.55-.82); however, clinician-reported scores were more consistently associated with the presence of physical impairments. CONCLUSIONS: In this population with stage IV breast cancer, ceiling effects limit the discriminatory capacity of the common functional scales assessed in this study. Instruments and items, particularly when ADL based, tend to perform better at lower levels of function (KPS 40-50) and less well at higher levels. Clinician-rated outcomes may have greater capacity to discriminate the presence of physical impairments.

BACKGROUND: Perineural invasion (PNI) has been associated with poor prognosis in cutaneous squamous cell carcinoma (CSCC), but it is unclear how different degrees of nerve involvement affect prognosis. OBJECTIVE: To determine whether the diameter of nerves invaded by CSCC affects outcomes of recurrence, metastasis, and disease-specific and overall survival. METHODS: A retrospective cohort study was conducted of patients with CSCC with PNI. Dermatopathologists blinded to subject outcomes determined the diameter of the largest involved nerve. RESULTS: Data were obtainable for 48 patients. Small-caliber nerve invasion (SCNI) of nerves less than 0.1 mm in diameter was associated with significantly lower risks of all outcomes of interest. Disease-specific death was 0% in subjects with SCNI, versus 32% in those with large-caliber nerve invasion (LCNI) (p=.003). Other factors associated with significantly worse survival were recurrent or poorly differentiated tumors or tumor diameter of 2 cm or greater or depth of 1 cm or greater. On multivariate analysis, only tumor diameter and age predicted survival. CONCLUSIONS: The individual prognostic significance of factors associated with poor survival remains uncertain. Small-caliber nerve invasion may not adversely affect outcomes. Defining PNI as tumor cells within the nerve sheath and routine recording of diameter of involved nerves, tumor depth, and histologic differentiation on pathology reports will facilitate further study.

A major obstacle in performing multicenter controlled trials for pemphigus is the lack of a validated disease activity scoring system. Here, we assess the reliability and convergent validity of the PDAI (pemphigus disease area index). A group of 10 dermatologists scored 15 patients with pemphigus to estimate the inter- and intra-rater reliability of the PDAI and the recently described ABSIS (autoimmune bullous skin disorder intensity score) instrument. To assess convergent validity, these tools were also correlated with the Physician's Global Assessment (PGA). Reliability studies demonstrated an intra-class correlation coefficient (ICC) for inter-rater reliability of 0.76 (95% confirdence interval (CI)=0.61-0.91) for the PDAI and 0.77 (0.63-0.91) for the ABSIS. The tools differed most in reliability of assessing skin activity, with an ICC of 0.39 (0.17-0.60) for the ABSIS and 0.86 (0.76-0.95) for the PDAI. Intra-rater test-retest reliability demonstrated an ICC of 0.98 (0.96-1.0) for the PDAI and 0.80 (0.65-0.96) for the ABSIS. The PDAI also correlated more closely with the PGA. We conclude that the PDAI is more reproducible and correlates better with physician impression of extent. Subset analysis suggests that for this population of mild-to-moderate disease activity, the PDAI captures more variability in cutaneous disease than the ABSIS

BACKGROUND & AIMS: In patients with chronic liver disease, race plays a role in the rate of survival after transplantation. It is not known how race and ethnicity influence the presentation, etiology, and outcomes in patients with acute liver failure (ALF). METHODS: A retrospective cohort study was conducted using the ALF Study Group database to assess differences between racial and ethnic groups in subjects with ALF. RESULTS: In the cohort of 927 subjects (81.8% white, 12.8% black, and 5.4% Asian), enrolled between January 1998 and March 2006, age, sex, and level of education were comparable among the groups. Differences were found in the prevalence of psychiatric illness and the use of medications. Racial groups also differed with respect to etiology of ALF. Whites presented more frequently with acetaminophen toxicity (51% vs 27%; P < .001). By day 21, 228 (30%) whites, 46 (39%) blacks, and 11 (22%) Asians had died. There were no significant differences found in the overall mortality rate after adjustment for potential confounders including etiology of ALF, encephalopathy, age, sex, admission laboratory values, and region. The odds of liver transplantation were higher among Asians and Hispanics; however, this finding was attenuated after adjustment for the previously-described confounders (adjusted odds ratio, 1.50; 95% confidence interval, 0.72-3.13; and adjusted odds ratio, 1.89; 95% confidence interval, 1.08-3.30, respectively). CONCLUSIONS: In patients with ALF, there were no significant differences in survival or rate of liver transplantation among racial and ethnic groups except for transplantation in Hispanics.

Psoriasis is a chronic Th-1 and Th-17 inflammatory disease. Chronic inflammation has also been associated with atherosclerosis and thrombosis. The purpose of this study was to determine the risk of stroke in patients with psoriasis. We conducted a population-based cohort study of patients seen by general practitioners participating in the General Practice Research Database in the United Kingdom, 1987-2002. Mild psoriasis was defined as any patient with a diagnostic code of psoriasis, but no history of systemic therapy. Severe psoriasis was defined as any patient with a diagnostic code of psoriasis and a history of systemic therapy consistent with severe psoriasis. The unexposed (control) population was composed of patients with no history of a psoriasis diagnostic code. When adjusting for major risk factors for stroke, both mild (hazard ratio (HR) 1.06, 95% confidence interval (CI) 1.0-1.1) and severe (1.43, 95% CI 1.1-1.9) psoriasis were independent risk factors for stroke. The excess risk of stroke attributable to psoriasis in patients with mild and severe disease was 1 in 4,115 per year and 1 in 530 per year, respectively. Patients with psoriasis, particularly if severe, have an increased risk of stroke that is not explained by major stroke risk factors identified in routine medical care.

BACKGROUND: Weight lifting has generally been proscribed for women with breast-cancer-related lymphedema, preventing them from obtaining the well-established health benefits of weight lifting, including increases in bone density. METHODS: We performed a randomized, controlled trial of twice-weekly progressive weight lifting involving 141 breast-cancer survivors with stable lymphedema of the arm. The primary outcome was the change in arm and hand swelling at 1 year, as measured through displaced water volume of the affected and unaffected limbs. Secondary outcomes included the incidence of exacerbations of lymphedema, number and severity of lymphedema symptoms, and muscle strength. Participants were required to wear a well-fitted compression garment while weight lifting. RESULTS: The proportion of women who had an increase of 5% or more in limb swelling was similar in the weight-lifting group (11%) and the control group (12%) (cumulative incidence ratio, 1.00; 95% confidence interval, 0.88 to 1.13). As compared with the control group, the weight-lifting group had greater improvements in self-reported severity of lymphedema symptoms (P=0.03) and upper- and lower-body strength (P<0.001 for both comparisons) and a lower incidence of lymphedema exacerbations as assessed by a certified lymphedema specialist (14% vs. 29%, P=0.04). There were no serious adverse events related to the intervention. CONCLUSIONS: In breast-cancer survivors with lymphedema, slowly progressive weight lifting had no significant effect on limb swelling and resulted in a decreased incidence of exacerbations of lymphedema, reduced symptoms, and increased strength. (ClinicalTrials.gov number, NCT00194363.)

PURPOSE: To evaluate inter- and intrareader agreement in breast percent density (PD) estimation on clinical digital mammograms and central digital breast tomosynthesis (DBT) projection images. MATERIALS AND METHODS: This HIPAA-compliant study had institutional review board approval; all patients provided informed consent. Breast PD estimation was performed on the basis of anonymized digital mammograms and central DBT projections in 39 women (mean age, 51 years; range, 31-80 years). All women had recently detected abnormalities or biopsy-proved cancers. PD was estimated by three experienced readers on the mediolateral oblique views of the contralateral breasts by using software; each reader repeated the estimation after 2 months. Spearman correlations of inter- and intrareader and intermodality PD estimates, as well as kappa statistics between categoric PD estimates, were computed. RESULTS: High correlation (rho = 0.91) was observed between PD estimates on digital mammograms and those on central DBT projections, averaged over all estimations; the corresponding kappa coefficient (0.79) indicated substantial agreement. Mean interreader agreement for PD estimation on central DBT projections (rho = 0.85 +/- 0.05 [standard deviation]) was significantly higher (P < .01) than that for PD estimation on digital mammograms (rho = 0.75 +/- 0.05); the corresponding kappa coefficients indicated substantial (kappa = 0.65 +/- 0.12) and moderate (kappa = 0.55 +/- 0.14) agreement for central DBT projections and digital mammograms, respectively. CONCLUSION: High correlation between PD estimates on digital mammograms and those on central DBT projections suggests the latter could be used until a method for PD estimation based on three-dimensional reconstructed images is introduced. Moreover, clinical PD estimation is possible with reduced radiation dose, as each DBT projection was acquired by using about 22% of the dose for a single mammographic projection.

OBJECTIVE: The goal was to compare the clinical effectiveness of monotherapy with beta-lactams, clindamycin, or trimethoprim-sulfamethoxazole in the outpatient management of nondrained noncultured skin and soft-tissue infections (SSTIs), in a methicillin-resistant Staphylococcus aureus (MRSA)-endemic region. METHODS: A retrospective, nested, case-control trial was conducted with a cohort of patients from 5 urban pediatric practices in a community-acquired MRSA-endemic region. All subjects were treated as outpatients with oral monotherapy for nondrained noncultured SSTIs between January 2004 and March 2007. The primary outcome was treatment failure, defined as a drainage procedure, hospitalization, change in antibiotic, or second antibiotic prescription within 28 days. RESULTS: Of 2096 children with nondrained noncultured SSTIs, 104 (5.0%) were identified as experiencing treatment failure and were matched to 480 control subjects. Compared with beta-lactam therapy, clindamycin was equally effective but trimethoprim-sulfamethoxazole was associated with an increased risk of failure. Other factors independently associated with failure included initial treatment in the emergency department, presence or history of fever, and presence of either induration or a small abscess. CONCLUSIONS: Compared with beta-lactams, clindamycin monotherapy conferred no benefit, whereas trimethoprim-sulfamethoxazole was associated with an increased risk of treatment failure in a cohort of children with nondrained noncultured SSTIs who were treated as outpatients. Even in regions with endemic community-acquired MRSA, beta-lactams may still be appropriate, first-line, empiric therapy for children presenting with these infections.

Lymphedema is a chronic and progressive long-term adverse effect of breast cancer treatment commonly defined by swelling of the affected arm. Current clinical guidelines indicate that women with and at risk for lymphedema should protect the affected arm from overuse. In clinical practice, this often translates into risk aversive guidance to avoid using the arm. This could lead to a disuse pattern that may increase the likelihood of injury from common activities of daily living. Further, such guidance poses an additional barrier to staying physically active, potentially translating to weight gain, which has been shown to be associated with worse clinical course for women with lymphedema. We hypothesize that a program of slowly progressive strength training with no upper limit on the amount of weight that may be lifted would gradually increase the physiologic capacity of the arm so that common activities represent a decreasing percentage of maximal capacity. Theoretically, this increased capacity should decrease the risk that daily activities put stress on the lymphatic system of the affected side. The Physical Activity and Lymphedema (PAL) Trial is a recently completed randomized controlled exercise intervention trial that recruited 295 breast cancer survivors (141 with lymphedema at study entry, 154 at risk for lymphedema at study entry). The purpose of this report is to provide detail regarding the study design, statistical design, and protocol of the PAL trial.

RATIONALE AND OBJECTIVES: Studies have demonstrated a relationship between mammographic parenchymal texture and breast cancer risk. Although promising, texture analysis in mammograms is limited by tissue superposition. Digital breast tomosynthesis (DBT) is a novel tomographic x-ray breast imaging modality that alleviates the effect of tissue superposition, offering superior parenchymal texture visualization compared to mammography. The aim of this study was to investigate the potential advantages of DBT parenchymal texture analysis for breast cancer risk estimation. MATERIALS AND METHODS: DBT and digital mammographic (DM) images of 39 women were analyzed. Texture features, shown in previous studies with mammograms to correlate with cancer risk, were computed from the retroareolar breast region. The relative performances of the DBT and DM texture features were compared in correlating with two measures of breast cancer risk: (1) the Gail and Claus risk estimates and (2) mammographic breast density. Linear regression was performed to model the association between texture features and increasing levels of risk. RESULTS: No significant correlation was detected between parenchymal texture and the Gail and Claus risk estimates. Significant correlations were observed between texture features and breast density. Overall, the DBT texture features demonstrated stronger correlations with breast percent density than DM features (P < or = .05). When dividing the study population into groups of increasing breast percent density, the DBT texture features appeared to be more discriminative, having regression lines with overall lower P values, steeper slopes, and higher R(2) estimates. CONCLUSION: Although preliminary, the results of this study suggest that DBT parenchymal texture analysis could provide more accurate characterization of breast density patterns, which could ultimately improve breast cancer risk estimation.