Training as an Intervention to Decrease Medical Record Abstraction Errors Multicenter Studies.

Studies often rely on medical record abstraction as a major source of data. However, data quality from medical record abstraction has long been questioned. Electronic Health Records (EHRs) potentially add variability to the abstraction process due to the complexity of navigating and locating study data within these systems. We report training for and initial quality assessment of medical record abstraction for a clinical study conducted by the IDeA States Pediatric Clinical Trials Network (ISPCTN) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN) using medical record abstraction as the primary data source. As part of overall quality assurance, study-specific training for medical record abstractors was developed and deployed during study start-up. The training consisted of a didactic session with an example case abstraction and an independent abstraction of two standardized cases. Sixty-nine site abstractors from thirty sites were trained. The training was designed to achieve an error rate for each abstractor of no greater than 4.93% with a mean of 2.53%, at study initiation. Twenty-three percent of the trainees exceeded the acceptance limit on one or both of the training test cases, supporting the need for such training. We describe lessons learned in the design and operationalization of the study-specific, medical record abstraction training program.

A nibbling mechanism for clathrin-mediated retrieval of secretory granule membrane after exocytosis.

Clathrin-mediated endocytosis is the major pathway for recycling of granule membrane components after strong stimulation and high exocytotic rates. It resembles "classical" receptor-mediated endocytosis but has a trigger that is unique to secretion, the sudden appearance of the secretory granule membrane in the plasma membrane. The spatial localization, the relationship to individual fusion events, the nature of the cargo, and the timing and nature of the nucleation events are unknown. Furthermore, a size mismatch between chromaffin granules (∼300-nm diameter) and typical clathrin-coated vesicles (∼90 nm) makes it unlikely that clathrin-mediated endocytosis internalizes as a unit the entire fused granule membrane. We have used a combination of total internal reflection fluorescence microscopy of transiently expressed proteins and time-resolved quantitative confocal imaging of endogenous proteins along with a fluid-phase marker to address these issues. We demonstrate that the fused granule membrane remains a distinct entity and serves as a nucleation site for clathrin- and dynamin-mediated endocytosis that internalizes granule membrane components in small increments.

A new role for the dynamin GTPase in the regulation of fusion pore expansion.

Dynamin is a master regulator of membrane fission in endocytosis. However, a function for dynamin immediately upon fusion has also been suspected from a variety of experiments that measured release of granule contents. The role of dynamin guanosine triphosphate hydrolase (GTPase) activity in controlling fusion pore expansion and postfusion granule membrane topology was investigated using polarization optics and total internal reflection fluorescence microscopy (pTIRFM) and amperometry. A dynamin-1 (Dyn1) mutant with increased GTPase activity resulted in transient deformations consistent with rapid fusion pore widening after exocytosis; a Dyn1 mutant with decreased activity slowed fusion pore widening by stabilizing postfusion granule membrane deformations. The experiments indicate that, in addition to its role in endocytosis, GTPase activity of dynamin regulates the rapidity of fusion pore expansion from tens of milliseconds to seconds after fusion. These findings expand the membrane-sculpting repertoire of dynamin to include the regulation of immediate postfusion events in exocytosis that control the rate of release of soluble granule contents.