Discovery of association rules in medical data

Data mining is a technique for discovering useful information from large databases. This technique is currently being profitably used by a number of industries. A common approach for information discovery is to identify association rules which reveal relationships among different items. In this paper, we use this approach to analyse a large database containing medical-record data. Our aim is to obtain association rules indicating relationships between procedures performed on a patient and the reported diagnoses. Random sampling was used to obtain these association rules. After reviewing the basic concepts associated with data mining, we discuss our approach for identifying association rules and report on the rules generated.     

In-vitro in-vivo correlation models for glibenclamide after administration of metformin/glibenclamide tablets to healthy human volunteers

In this study, level C and A in-vitro in-vivo correlation (IVIVC) models were developed for glibenclamide. In-vitro dissolution data were collected for the glibenclamide component of three metformin/glibenclamide tablets using a USP Type II apparatus. In-vivo plasma concentration data were obtained after administration of the prototype formulations to 24 healthy volunteers and subject to deconvolution analysis to obtain percentage in-vivo absorbed profiles. Multiple linear level C models were developed for CMAX and AUC(0-48) using percentage in-vitro dissolved data at 10, 45 and 120 min. Initially, the level A model was constructed for the first 2 h only, based on availability of in-vitro data. Another level A model was attempted using a time-scaled approach, with percentage in-vivo absorbed at time t and percentage in-vitro dissolved at time t/I as the correlating data. Internal predictability was evaluated for the level C and time-scaled level A models. For all level C approaches, linear regression models with r2 > 0.99 were determined. The prediction errors (% PE) for Cmax and AUC(0-48) were less than 1% for all formulations at all three chosen time points. The deconvolution analysis indicated biphasic absorption for glibenclamide, with one phase occurring at 2-3h and another at 6-12h after dose administration. The level A model using 2-h data was not unique for all formulations and was therefore not developed. The time-scaling factor I correlated highly (r2 = 0.99) with in vitro mean dissolution time (MDT). A linear regression time scaled model (r2 = 0.97) was successfully developed using in-vitro and in-vivo data from all 3 formulations. However, the internal predictability of the time-scaled model was poor, with % PE values for Cmax and AUC(0-48) being as much as 30.5% and 18.7%, respectively. The results indicate that level C models have good internal predictability. Though a time-scaled level A IVIVC model was successfully developed, the model was found to have poor internal predictability.     

A novel semi-mechanistic tumor growth fraction model for translation of preclinical efficacy of anti-glypican 3 antibody drug conjugate to human

The growing fraction (GF) of tumor has been reported as one of the predictive markers of the efficacy of chemotherapeutics. Therefore, a semi-mechanistic model has been developed that describes tumor growth on the basis of cell cycle, allowing the incorporation of the GF of a tumor in pharmacokinetic/pharmacodynamic (PK/PD) modeling. Efficacy data of anti-glypican 3 (GPC3) antibody drug conjugate (ADC) in a hepatocellular carcinoma (HCC) patient derived xenograft (PDX) model was used for evaluation of this proposed model. Our model was able to describe the kinetics of growth inhibition of HCC PDX models following treatment with anti-GPC3 ADC remarkably well. The estimated tumurostatic concentrations were used in tandem with human PKs translated from cynomolgus monkey for prediction of the efficacious dose. The projected efficacious human dose of anti-GPC3 ADC was in the range 0.20–0.63 mg/kg for the Q3W dosing regimen, with a median dose of 0.50 mg/kg. This publication is the first step in evaluating the applicability of GF in PK/PD modeling of ADCs. The authors are hopeful that incorporation of GF will result in an improved translation of the preclinical efficacy of ADCs to clinical settings and thereby better prediction of the efficacious human dose.     

Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays

A series of substituted 2-(aminopyridyl)- and 2-(aminopyrimidinyl)thiazole-5-carboxamides was identified as potent Src/Abl kinase inhibitors with excellent antiproliferative activity against hematological and solid tumor cell lines. Compound 13 was orally active in a K562 xenograft model of chronic myelogenous leukemia (CML), demonstrating complete tumor regressions and low toxicity at multiple dose levels. On the basis of its robust in vivo activity and favorable pharmacokinetic profile, 13 was selected for additional characterization for oncology indications.     

Care Coordination Associated with Improved Timing of Newborn Primary Care Visits

Objective Despite practice recommendations that all newborns be examined within 3–5 days after discharge, many are not seen within this timeframe. Our objective was to determine the association between care coordination and timing of newborn follow-up. Methods This retrospective study evaluated 6251 newborns from eight maternity hospitals who scheduled a primary care appointment at one of two academic pediatric practices over 3.5 years. Two programs were sequentially implemented: (1) newborn discharge coordination, and (2) primary care intake coordination. Primary outcome was days between discharge and follow-up, dichotomized as ≤ or >5 days. Number of rescheduled appointments and loss to follow-up were also assessed. Adjusted relative risks (RR) and odds ratios (OR) were determined by piecewise generalized linear and logistic regression. Results Among 5943 newborns with a completed visit, 52.9 % were seen within 5 days of discharge (mean 6.7 days). After multivariable adjustment, the pre-exposure period (8 months) demonstrated a downward monthly trend in completing early follow-up (RR 0.93, p < 0.001). After initial program implementation, we observed a 3 % monthly increase (RR 1.03, p < 0.001 for test of slope change from pre-exposure to post-exposure), such that likelihood of recommended follow-up increased by roughly 72 % after discharge coordinator implementation and roughly 33 % after primary care coordinator implementation. The latter was also associated with a 13 % monthly decrease in odds of loss to follow-up (OR 0.87, p < 0.001). Conclusions for Practice Care coordination increases adherence among low income families to recommended newborn follow-up after birth hospitalization.     

Effects of pyridoxine on implantation and pregnancy in Wistar rat

Pyridoxine hydrochloride was gavaged to 2 groups of pregnant Wistar rats from day 0 to 13 and day 6 to 15 of gestation at doses of 100, 200, 400 and 800 mg/kg. A higher number of implantations, live pups and corpora lutea were observed in the treated rats, but a significant reduction in the body weights of the pups was noticed in the groups treated with 400 and 800 mg/kg. No other adverse effects on implantation and pregnancy were noticed. No evidence of dismorphogenic effects was seen.     

Estimation of the aqueous solubility of weak electrolytes

Jain and Yalkowsky [Jain, N., Yalkowsky, S.H., 2001. Estimation of the aqueous solubility. I. Application to organic non-electrolytes. J. Pharm. Sci. 90, 234-252.] demonstrated that the general solubility equation (GSE) can be used to estimate the aqueous solubility of organic non-electrolytes. In this study the applicability of the GSE was extended to weak electrolytes. It is demonstrated that the GSE estimates the aqueous solubility of 949 compounds, including 367 weak electrolytes with an AAE of 0.58. It is also shown that the intrinsic solubilities of weak acids for which the pK(a)+log S(w)相似文献   

Wash resistance and efficacy of Olyset net and Permanet 2.0 against Anopheles stephensi in India

Long-lasting insecticidal nets (LLIN) have been developed for wash resistance and long-lasting effects against mosquito vectors. In this study we evaluated 2 LLIN products, Olyset net and Permanet 2.0, washed for 0, 5, 10, 15, and 20 times, against Anopheles stephensi, an urban malaria vector in India. We assessed the wash resistance and efficacy of these nets in relation to bloodfeeding inhibition and percent mortality in cone and tunnel test bioassays. Both Olyset and Permanet showed >80% mortality of An. stephensi in cone bioassays after 20 washes. In tunnel tests there was no significant difference between Olyset and Permanet 2.0 in causing total mosquito mortality (immediate and delayed) up to 10 washes and bloodfeeding inhibition and entry rate up to 15 washes. After the 20th wash, Permanet 2.0 was significantly more effective than the Olyset net in causing total mosquito mortality, whereas Olyset net showed less bloodfeeding and entry of mosquitoes as compared to Permanet 2.0. There was a gradual decline in efficacy of both LLIN products as the number of washings increased. Cone bioassays indicated a strong wash resistance in both the LLIN products after 20 washes. However, the tunnel tests demonstrated a gradual decline in efficacy of both products with the number of washings.