‘Outbreak Gold Standard’Selection to Provide Optimized Threshold for Infectious Diseases Early-alert Based on China Infectious Disease Automated-alert and Response System

The China Infectious Disease Automated-alert and Response System（CIDARS） was successfully implemented and became operational nationwide in 2008. The CIDARS plays an important role in and has been integrated into the routine outbreak monitoring efforts of the Center for Disease Control（CDC） at all levels in China. In the CIDARS, thresholds are determined using the ？Mean＋2SD？ in the early stage which have limitations. This study compared the performance of optimized thresholds defined using the ？Mean ＋2SD？ method to the performance of 5 novel algorithms to select optimal ？Outbreak Gold Standard（OGS）？ and corresponding thresholds for outbreak detection. Data for infectious disease were organized by calendar week and year. The ？Mean＋2 SD？, C1, C2, moving average（MA）, seasonal model（SM）, and cumulative sum（CUSUM） algorithms were applied. Outbreak signals for the predicted value（Px） were calculated using a percentile-based moving window. When the outbreak signals generated by an algorithm were in line with a Px generated outbreak signal for each week, this Px was then defined as the optimized threshold for that algorithm. In this study, six infectious diseases were selected and classified into TYPE A（chickenpox and mumps）, TYPE B（influenza and rubella） and TYPE C [hand foot and mouth disease（HFMD） and scarlet fever]. Optimized thresholds for chickenpox（P_（55））, mumps（P_（50））, influenza（P_（40）, P_（55）, and P_（75））, rubella（P_（45） and P_（75））, HFMD（P_（65） and P_（70））, and scarlet fever（P_（75） and P_（80）） were identified. The C1, C2, CUSUM, SM, and MA algorithms were appropriate for TYPE A. All 6 algorithms were appropriate for TYPE B. C1 and CUSUM algorithms were appropriate for TYPE C. It is critical to incorporate more flexible algorithms as OGS into the CIDRAS and to identify the proper OGS and corresponding recommended optimized threshold by different infectious disease types.

Application of RP-HPLC method in dissolution testing and statistical evaluation by NASSAM for simultaneous estimation of tertiary combined dosages forms

A dissolution method with robust high performance liquid chromatographic （HPLC） analysis for im- mediate release tablet formulation was developed and validated to meet the requirement as per Inter- national Conference on Harmonization （ICH） and United States Food and Drug Administration （USFDA） guidelines. The method involved the use of Agilent ZORBAX Eclipse XDB C18 column, and temperature was maintained at 30 ℃. After optimization, the mobile phase was selected as phosphate buffer （KH2PO4, 30 mM） ： ACN （60：40, v/v） with pH 3.0, and retention time Rt was found as 3.24, 4.16, and 2.55 min for paracetamol （PCM）, chlorpheniramine maleate （CPM） and phenylephrine hydrochloride （PH） respec- tively at 265 nm and at a flow rate of 1 mL/min. The relative standard deviation （%RSD） for 6 replicate measurements was found to be less than 2%. Furthermore net analyte signal standard addition method （NASSAM） with spectrophotometer was performed for standard and liquid oral suspension. On the basis of selectivity, sensitivity and accuracy analysis, it was confirmed that this novel method could be useful for simultaneous estimation of the given drug combinations. Two-way analysis of variance （ANOVA） was applied for evaluating the statistical difference between the assay results obtained via both NASSAM and RP-HPLC methods and ultimately no significant difference was found between both the methods. All the methods and results were acceptable and confirmed that the method was suitable for intended use.