RESUMO
PURPOSE: Use of administrative or population-based databases for post-marketing pharmacoepidemiology research in patients with end-stage liver disease (ESLD) has been limited by the difficulty of accurately identifying such patients. Algorithms to identify patients with ESLD using ICD-9-CM codes have not been developed outside of the Veterans Affairs healthcare setting. METHODS: We queried electronic medical records at two tertiary care hospitals to identify patients with ICD-9-CM codes indicative of ESLD. Coding algorithms were developed to identify patients with confirmed ESLD, and these were tested to determine their positive predictive value (PPV). RESULTS: The presence of one inpatient or outpatient ICD-9-CM code for: (i) cirrhosis; (ii) chronic liver disease, and (iii) a hepatic decompensation event yielded a PPV of 85.2% (167/196; 95% CI: 79.4%-89.9%). The PPV increased to 89.3% (150/168; 95% CI: 83.6%-93.5%) when the algorithm required two or more ICD-9-CM codes for a hepatic decompensation. However, an algorithm requiring only one ICD-9-CM code for (i) cirrhosis and (ii) a hepatic decompensation event, in the absence of a chronic liver disease code, yielded a PPV of 85.7% (30/35; 95% CI: 69.7%-95.2%). CONCLUSIONS: A coding algorithm that includes at least one ICD-9-CM code for cirrhosis plus one ICD-9-CM code for a hepatic decompensation event has a high PPV for identifying patients with ESLD. The inclusion of at least two codes indicative of a hepatic decompensation event increased the PPV. This algorithm can be used in future epidemiologic studies to examine the outcomes of a variety of long-term medical therapies in patients with ESLD. Copyright © 2012 John Wiley & Sons, Ltd.
RESUMO
The kinetics of soluble aggregate formation in equine IgG was studied in the pH 3.4-4.3 range and ionic strength between 0.02 and 0.5 M, and a diagram describing aggregation kinetics as diffusion limited, reaction limited, or transitional as a function of pH and ionic strength was constructed. Aggregation rate is limited by the degree of electrostatic repulsion between the protein molecules in the pH 4.0-4.5 range. Below pH 4.0, a greater degree of attractive force is present, most likely from protein unfolding, and electrostatic repulsion no longer determines the rate of aggregation. The aggregation rate increases with decreasing pH, and at pH 3.4 the aggregation rate is diffusion limited. The pH range separating reaction-limited and diffusion-limited kinetics decreases with increasing ionic strength, indicating charge shielding from the buffer solution influences the aggregation rate. Copyright 1997 Academic Press.
