Nonbullous neutrophilic lupus erythematosus: a newly recognized variant of cutaneous lupus erythematosus.

BACKGROUND: Neutrophils in the setting of systemic lupus erythematosus (SLE) are commonly associated with bullous disease. Rare cases of nonbullous neutrophilic lesions have been reported in patients with SLE. OBJECTIVE: This study used clinical and histologic findings of 4 patients to further define the newly emerging entity of nonbullous neutrophilic lupus erythematosus (LE). METHODS: We reviewed the clinical and pathological findings of 4 patients with known SLE who developed urticarial papules, plaques, subcutaneous nodules, or a combination of these. RESULTS: All patients were women with established SLE. Histopathological findings in all patients included an interstitial and perivascular neutrophilic infiltrate with leukocytoclasia, and variable vacuolar alteration along the dermoepidermal junction. Direct immunofluorescence study results in two patients were positive for C3, IgG, and IgM along the basement membrane zone. One patient also presented with neutrophil-rich lupus panniculitis. All clinical lesions resolved with immunomodulating/immunosuppressive agents. LIMITATIONS: This study was limited by the small number of cases. CONCLUSIONS: Nonbullous neutrophilic LE is an important entity to consider in the differential diagnosis of neutrophil-mediated eruptions. In addition, the histologic finding of neutrophils in the setting of lupus should alert one to the possibility of systemic disease.

Characterization of a monoclonal antibody cell culture production process using a quality by design approach.

The goal of quality by design (QbD) in cell culture manufacturing is to develop manufacturing processes which deliver products with consistent critical quality attributes (CQAs). QbD approaches can lead to better process understanding through the use of process parameter risk ranking and statistical design of experiments (DOE). The QbD process starts with an analysis of process parameter risk with respect to CQAs and key performance indicators (KPIs). Initial DOE study designs and their factor test ranges are based on the outcomes of the process parameter risk ranking exercises. Initial DOE studies screen factors for significant influences on CQAs as well as characterize responses for process KPIs. In the case study provided here, multifactor process characterization studies using a scale-down model resulted in significant variation in charge heterogeneity of a monoclonal antibody (MAb) as measured by ion-exchange chromatography (IEC). Iterative DOE studies, using both screening and response surface designs, were used to narrow the operating parameter ranges so that charge heterogeneity could be controlled to an acceptable level. The data from the DOE studies were used to predict worst-case conditions, which were then verified by testing at those conditions. Using the approach described here, multivariate process parameter ranges were identified that yield acceptable CQA levels and that still provide operational flexibility for manufacturing.

Dynamics of patient targeting for care management in Medicaid: a case study of the Durham Community Health Network.

Targeting appropriate patients for care management is crucial to maximizing quality of care and cost-effectiveness in Medicaid care management programs. This study examined patient characteristics predicting selection for care management pre- and postmanagement changes at the Durham Community Health Network (DHCN), one of North Carolina's Medicaid primary care management networks. From the beginning, care managers were directed to target asthmatics, diabetics, and high-volume utilizers of health care, using an array of markers to identify patients who needed management. In 2003, the state reinforced its focus on chronic disease and high utilizers, and new management at DCHN began emphasizing the use of protocols for patient targeting. This study examined the relative effects of patient demographics, diagnoses, PCP group, and health care utilization as predictors of patient selection before and after these changes.