Faculty Bibliography

OBJECTIVE: To determine how to use the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) to classify patients according to disease severity (mild, moderate, and severe) and to identify which patients respond to therapy. DESIGN: Cohort. SETTING: The connective-tissue disease clinic at the Hospital of the University of Pennsylvania, Philadelphia. PATIENTS: Seventy-five patients with clinical or histopathologic evidence of cutaneous lupus erythematosus or systemic lupus erythematosus were included in the study. MAIN OUTCOME MEASURES: The CLASI, Skindex-29, and the physician's subjective assessment of severity and improvement were completed at every visit. RESULTS: Disease severity was assessed with 45 patient visits. Mild, moderate, and severe disease corresponded with CLASI activity score ranges of 0 to 9, 10 to 20, and 21 to 70, respectively. Improvement in disease activity was assessed in 74 patients. A clinical improvement was associated with a mean 3-point or 18% decrease in the CLASI activity score. However, receiver operating characteristic analysis demonstrated an increased percentage of patients correctly classified when a 4-point (sensitivity, 39%; specificity, 93%; correctly classified, 76%) or 20% (sensitivity, 46%; specificity, 78%; correctly classified, 67%) decrease in the CLASI activity score was used instead to identify improvement. CONCLUSION: The CLASI can be used to classify patients into groups according to disease severity and to identify clinically significant improvements in disease activity.

CONTEXT: Clinical guidelines for breast cancer survivors without lymphedema advise against upper body exercise, preventing them from obtaining established health benefits of weight lifting. OBJECTIVE: To evaluate lymphedema onset after a 1-year weight lifting intervention vs no exercise (control) among survivors at risk for breast cancer-related lymphedema (BCRL). DESIGN, SETTING, AND PARTICIPANTS: A randomized controlled equivalence trial (Physical Activity and Lymphedema trial) in the Philadelphia metropolitan area of 154 breast cancer survivors 1 to 5 years postunilateral breast cancer, with at least 2 lymph nodes removed and without clinical signs of BCRL at study entry. Participants were recruited between October 1, 2005, and February 2007, with data collection ending in August 2008. INTERVENTION: Weight lifting intervention included a gym membership and 13 weeks of supervised instruction, with the remaining 9 months unsupervised, vs no exercise. MAIN OUTCOME MEASURES: Incident BCRL determined by increased arm swelling during 12 months (>/=5% increase in interlimb difference). Clinician-defined BCRL onset was also evaluated. Equivalence margin was defined as doubling of lymphedema incidence. RESULTS: A total of 134 participants completed follow-up measures at 1 year. The proportion of women who experienced incident BCRL onset was 11% (8 of 72) in the weight lifting intervention group and 17% (13 of 75) in the control group (cumulative incidence difference [CID], -6.0%; 95% confidence interval [CI], -17.2% to 5.2%; P for equivalence = .04). Among women with 5 or more lymph nodes removed, the proportion who experienced incident BCRL onset was 7% (3 of 45) in the weight lifting intervention group and 22% (11 of 49) in the control group (CID, -15.0%; 95% CI, -18.6% to -11.4%; P for equivalence = .003). Clinician-defined BCRL onset occurred in 1 woman in the weight lifting intervention group and 3 women in the control group (1.5% vs 4.4%, P for equivalence = .12). CONCLUSION: In breast cancer survivors at risk for lymphedema, a program of slowly progressive weight lifting compared with no exercise did not result in increased incidence of lymphedema. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00194363.

BACKGROUND: Severe psoriasis is associated with excess mortality and increased risk of cardiovascular death. Population-based data evaluating cause-specific mortality in patients with psoriasis are limited. OBJECTIVES: To describe cause-specific mortality in patients with severe psoriasis. METHODS: We performed a cohort study from 1987 to 2002 of patients >/=18 years using the General Practice Research Database. We compared patients with a psoriasis code and a history of systemic therapy consistent with severe psoriasis (n=3603) with patients with no history of psoriasis (n=14,330). Age- and sex-adjusted Cox models were created for each of the leading causes of death defined by the Centers for Disease Control. RESULTS: Patients with severe psoriasis were at increased risk of death from cardiovascular disease [hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.26-1.96], malignancies (HR 1.41, 95% CI 1.07-1.86), chronic lower respiratory disease (HR 2.08, 95% CI 1.24-3.48), diabetes (HR 2.86, 95% CI 1.08-7.59), dementia (HR 3.64, 95% CI 1.36-9.72), infection (HR 1.65, 95% CI 1.26-2.18), kidney disease (HR 4.37, 95% CI 2.24-8.53) and unknown/missing causes (HR 1.43, 95% CI 1.09-1.89). The absolute and excess risk of death was highest for cardiovascular disease (61.9 and 3.5 deaths per 1000 patient-years, respectively). CONCLUSIONS: Severe psoriasis is associated with an increased risk of death from a variety of causes, with cardiovascular death being the most common aetiology. These patients were also at increased risk of death from causes not previously reported, such as infection, kidney disease and dementia. Additional studies are necessary to determine the degree to which excess causes of death are due to psoriasis, its treatments, associated behaviours, or other factors

OBJECT: The object of this study was to determine whether brain tissue oxygen (PbtO(2))-based therapy or intracranial pressure (ICP)/cerebral perfusion pressure (CPP)-based therapy is associated with improved patient outcome after severe traumatic brain injury (TBI). METHODS: Seventy patients with severe TBI (postresuscitation GCS score < or = 8), admitted to a neurosurgical intensive care unit at a university-based Level I trauma center and tertiary care hospital and managed with an ICP and PbtO(2) monitor (mean age 40 +/- 19 years [SD]) were compared with 53 historical controls who received only an ICP monitor (mean age 43 +/- 18 years). Therapy for both patient groups was aimed to maintain ICP < 20 mm Hg and CPP > 60 mm Hg. Patients with PbtO(2) monitors also had therapy to maintain PbtO(2) > 20 mm Hg. RESULTS: Data were obtained from 12,148 hours of continuous ICP monitoring and 6,816 hours of continuous PbtO(2) monitoring. The mean daily ICP and CPP and the frequency of elevated ICP (> 20 mm Hg) or suboptimal CPP (< 60 mm Hg) episodes were similar in each group. The mortality rate was significantly lower in patients who received PbtO(2)-directed care (25.7%) than in those who received conventional ICP and CPP-based therapy (45.3%, p < 0.05). Overall, 40% of patients receiving ICP/CPP-guided management and 64.3% of those receiving PbtO(2)-guided management had a favorable short-term outcome (p = 0.01). Among patients who received PbtO(2)-directed therapy, mortality was associated with lower mean daily PbtO(2) (p < 0.05), longer durations of compromised brain oxygen (PbtO(2) < 20 mm Hg, p = 0.013) and brain hypoxia (PbtO(2) < 15 mm Hg, p = 0.001), more episodes and a longer cumulative duration of compromised PbtO(2) (p < 0.001), and less successful treatment of compromised PbtO(2) (p = 0.03). CONCLUSIONS: These results suggest that PbtO(2)-based therapy, particularly when compromised PbtO(2) can be corrected, may be associated with reduced patient mortality and improved patient outcome after severe TBI.

OBJECTIVES: To evaluate the effects of race on QOL while adjusting for subjective stress and religiosity among African American and white prostate cancer patients. Although racial differences in quality of life (QOL) have been examined between African American and white prostate cancer patients, it is not known whether differences exist while adjusting for psychological and cultural factors. We predicted that African American men would report poorer emotional and physical functioning after adjusting for these factors and that greater subjective stress and lower levels of religiosity would be associated with poorer well-being. METHODS: We conducted an observational study of QOL among 194 African American and white men who were recruited from February 2003 through March 2008. RESULTS: Race had a significant effect on emotional functioning after adjusting for perceptions of stress and religiosity. Compared with white men, African American men (P = .03) reported significantly greater emotional well-being. Greater subjective stress was associated significantly with poorer emotional functioning (P = .0001) and physical well-being (P = .0001). There were no racial differences in physical functioning (P = .76). CONCLUSIONS: The results of this study highlight the importance of developing a better understanding of the context within which racial differences in QOL occur and translating this information into support programs for prostate cancer survivors.

OBJECTIVE: To determine the incidence of depression, anxiety, and suicidality in patients with psoriasis compared with the general population. DESIGN: A population-based cohort study using data collected as part of patient's electronic medical record from 1987 to 2002. SETTING: General Practice Research Database. PATIENTS: Analyses included 146 042 patients with mild psoriasis, 3956 patients with severe psoriasis, and 766 950 patients without psoriasis. Five controls without psoriasis were selected from the same practices and similar cohort entry dates as patients with psoriasis. MAIN OUTCOME MEASURE: Clinical diagnoses of depression, anxiety, and suicidality among patients. RESULTS: The adjusted hazard ratios (HRs) for receiving a diagnosis of depression, anxiety, and suicidality in patients with psoriasis compared with controls were 1.39 (95% confidence interval [CI], 1.37-1.41), 1.31 (95% CI, 1.29-1.34), and 1.44 (95% CI, 1.32-1.57), respectively. The adjusted HR of depression was higher in severe (HR, 1.72; 95% CI, 1.57-1.88) compared with mild psoriasis (HR, 1.38; 95% CI, 1.35-1.40). Younger patients with psoriasis had elevated HRs of outcomes compared with older patients with psoriasis. CONCLUSIONS: Patients with psoriasis have an increased risk of depression, anxiety, and suicidality. We estimate that in the United Kingdom, in excess of 10 400 diagnoses of depression, 7100 diagnoses of anxiety, and 350 diagnoses of suicidality are attributable to psoriasis annually. It is important for clinicians to evaluate patients with psoriasis for these conditions to improve outcomes. Future investigation should determine the mechanisms by which psoriasis is associated with psychiatric outcomes as well as approaches for prevention.

For longitudinal binary data with non-monotone non-ignorably missing outcomes over time, a full likelihood approach is complicated algebraically, and with many follow-up times, maximum likelihood estimation can be computationally prohibitive. As alternatives, two pseudo-likelihood approaches have been proposed that use minimal parametric assumptions. One formulation requires specification of the marginal distributions of the outcome and missing data mechanism at each time point, but uses an 'independence working assumption,' i.e. an assumption that observations are independent over time. Another method avoids having to estimate the missing data mechanism by formulating a 'protective estimator.' In simulations, these two estimators can be very inefficient, both for estimating time trends in the first case and for estimating both time-varying and time-stationary effects in the second. In this paper, we propose the use of the optimal weighted combination of these two estimators, and in simulations we show that the optimal weighted combination can be much more efficient than either estimator alone. Finally, the proposed method is used to analyze data from two longitudinal clinical trials of HIV-infected patients.