Investigating Serious Adverse Drug Reactions in Patients Receiving Erythropoiesis-Stimulating Agents: A Root Cause Analysis Using the "ANTICIPATE" Framework.

BACKGROUND: Unexpected serious adverse drug reactions (sADRs) affecting patients with chronic kidney disease (CKD) who received erythropoiesis-stimulating agents were identified by study co-authors. These included pure red cell aplasia (PRCA) after administration of the Eprex formulation of epoetin or the epoetin biosimilar HX575 and fatal anaphylaxis associated with peginesatide, an erythropoietin receptor agonist. We developed and applied a structured framework to describe these sADRs, including root cause analyses and eradication efforts. METHODS: A 10-step framework termed "ANTICIPATE," focusing on signal identification, incidence, causality, and eradication guided our evaluations. RESULTS: Initial cases were identified by a hematologist (Eprex), clinical study monitors (HX575), and 4 nurses (peginesatide). The number of persons with individual ADRs was 13 PRCA cases for epoetin, 2 antibody-mediated PRCA cases for HX575, and 5 fatal anaphylaxis cases for peginesatide. Initial incidence estimates per 1000 treated persons were 0.27 for Eprex-associated PRCA, 11 for HX575-associated PRCA, and 0.38 for peginesatide fatalities. Likely causes were subcutaneous administration of epoetin formulated with polysorbate 80 (Eprex), tungsten leaching from pins included in product syringes (HX575), and inclusion of a phenol stabilizer (peginesatide). Eradication strategies included restricting Eprex administration to the intravenous route, excluding tungsten from HX575 syringes, and for peginesatide, proposed eradication was to return to single-dose vials without preservatives. CONCLUSION: Although the number of cases of each sADR was small, eradication was successful for 2 sADRs, and a proposed eradication was developed for a third sADR. The structured framework used to describe the above 3 sADRs in patients with CKD can also be used in other clinical settings.

Hydrophobic treatment enabling analysis of wettable surfaces using a liquid microjunction surface sampling probe/electrospray ionization-mass spectrometry system.

An aerosol application procedure involving one or more commercially available silicone-based products was developed to create hydrophobic surfaces that enable analysis of otherwise wettable, absorbent surfaces using a liquid microjunction surface sampling probe/electrospray ionization mass spectrometry system. The treatment process resulted in a hydrophobic surface that enabled formation of the requisite probe-to-surface liquid microjunction for sampling and allowed efficient extraction of the analytes from the surface, but did not contribute significant chemical background in the mass spectra. The utility of this treatment process was demonstrated with the treatment of wettable high-performance thin layer chromatography plates, post-plate development, and their subsequent analysis with the sampling probe. The surface treatment process for different surface types was described and explained and the effectiveness of the treatment and subsequent analysis was illustrated using alkaloids from goldenseal (Hydrastis canadensis) root separated on a normal phase silica gel 60 F(254S) plate and peptides from protein tryptic digests separated on a ProteoChrom HPTLC Silica gel 60 F(254S) plate and a ProteoChrom HPTLC Cellulose sheet. This simple surface treatment process significantly expands the analytical surfaces that can be analyzed with the liquid microjunction surface sampling probe, and therefore, also expands the analytical utility of this liquid extraction based surface sampling approach.

New districts--old results?

On Nov. 5, Michigan voters will elect legislators in each of Michigan's 15 new congressional districts to serve in Washington, DC, as well as state senators and representatives from newly drawn districts. But will the new districts change the makeup of the congressional delegation and the Republican's decade-long hold on majorities in the state House and Senate?