Exaggerated or inappropriate responses by B cells are an important feature in many types of autoimmune neurological diseases. The recent success of B-cell depletion in the treatment of multiple sclerosis (MS) has stimulated the development of novel B-cell-targeting therapies with the potential for improved efficacy. CD19 has emerged as a promising target for the depletion of B cells as well as CD19-positive plasmablasts and plasma cells. Inebilizumab (MEDI-551), an anti-CD19 antibody with enhanced antibody-dependent cell-mediated cytotoxicity against B cells, is currently being evaluated in MS and neuromyelitis optica. This review discusses the role of B cells in autoimmune neurological disorders, summarizes the development of inebilizumab, and analyzes the recent results for inebilizumab treatment in an autoimmune encephalitis mouse model. The novel insights obtained from these preclinical studies can potentially guide future investigation of inebilizumab in patients.

The teaching and guideline intervention improved the quality and reduced the quantity of antimicrobial use in LTC patients.

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BackgroundLittle is known about the effect of provider continuity prior to the diagnosis of advanced lung cancer and end-of-life care.MethodsRetrospective analysis of 69,247 Medicare beneficiaries aged 67 years or older diagnosed with Stage IIIB or IV lung cancer between January 1, 1993 and December 31, 2005 who died within two years of diagnosis. We examined visit patterns to a primary care physician (PCP) and/or any provider one year prior to the diagnosis of advanced lung cancer as measures of continuity of care. Outcome measures were hospitalization, ICU use and chemotherapy use during the last month of life, and hospice use during the last week of life.ResultsSeeing a PCP or any provider in the year prior to the diagnosis of advanced lung cancer increased the likelihood of hospitalization, ICU care, chemotherapy and hospice use during the end of life. Patients with 1–3, 4–7 or >7 visits to their PCP in the year prior to the diagnosis of lung cancer had 1.0 (reference), 1.08 (95% CI; 1.04–1.13), and 1.14 (95% CI; 1.08–1.19) odds of hospitalization during the last month of life, respectively. Odds of hospice use during the last week of life were higher in patients with visits to multiple PCPs (OR 1.10: 95% CI; 1.06–1.15) compared to those whose visits were all to the same PCP.ConclusionProvider continuity in the year prior to the diagnosis of advanced lung cancer was not associated with lower use of aggressive care during end of life. Our study did not have information on patient preferences and result should be interpreted accordingly.

The quest of geological proxies to evaluate low-latitude hydrological changes at a planetary scale remains an ongoing issue. The Dole effect is such a potential proxy owing to its global character. We propose a new approach to recalculate the fluctuation of the Dole effect (∆DE*) over the past 800 thousand years (ka). The ∆DE* calculated this way is dominated by precession cycles alone, with lesser variance in the obliquity bands and almost no variance in the eccentricity bands. Moreover, the ∆DE* is notably correlated with Chinese stalagmite δ18O record over the past 640 ka; simulated terrestrial rainfall changes between 30°N and 30°S over the past 300 ka. Our findings highlight the predominant role of the low-latitude hydroclimate in governing the ∆DE* on orbital time scales, while high-latitude climate impacts are negligible. In turn, we argue that the ∆DE* can be used to indicate low-latitude hydrological changes at a global extent.