Lower Risk of Major Cardiovascular Events Associated With Adherence to Colesevelam HCI.

Lower Risk of Major Cardiovascular Events Associated with Adherence to Colesevelam HCI.

Pharmacotherapy. 2013 Jun 24;
Ye X, Qian C, Liu J, St Peter WL

To examine the relationship between adherence to colesevelam and the risk of major cardiovascular events (acute myocardial infarction [AMI] and stroke) among patients newly treated with colesevelam.Retrospective cohort study using administrative claims data.MarketScan commercial and Medicare databases (2005-2011).A total of 42,549 adults with hyperlipidemia and/or type 2 diabetes mellitus who newly started colesevelam between January 1, 2005, and September 30, 2011, and who had continuous enrollment in employer-sponsored commercial health insurance or Medicare supplemental benefit plans for at least 6 months before and 12 months after the date of colesevelam initiation.Adherence was measured as the proportion of days covered (PDC) by prescription claims for colesevelam during the 1-year period after the drug initiation date. Patients were assigned to one of three adherence cohorts: adherent, PDC of 0.8 or more; partially adherent,PDC of 0.5-0.8; or nonadherent, PDC of less than 0.5. The primary outcome was time to the first hospitalization with a primary diagnosis for AMI or stroke during the follow-up period. Association of colesevelam adherence with the primary outcome was examined by multivariate Cox regression models, adjusting for demographics, comorbidity, and concomitant drugs. A sensitivity analysis between propensity score-matched cohorts was conducted to compare the outcome between adherent and nonadherent groups. Of the 42,549 patients included in the analysis, 7968 (18.7%) were adherent, 6197 (14.6%) were partially adherent, and 28,384 (66.7%) were nonadherent. Compared with nonadherent patients, adherent patients were older, more likely to be male and from the Northeast or North Central regions of the United States, and had more cardiovascular risk factors and concomitant drugs. Controlling for patient demographic and clinical characteristics, adherent patients were about 43% less likely to experience an AMI or stroke hospitalization during the follow-up period compared with nonadherent patients (hazard ratio 0.57, 95% confidence interval[CI] 0.44-0.73, p<0.0001). Results of the sensitivity analysis using propensity score matching techniques were consistent.Adherence to colesevelam was associated with lower risk of major cardiovascular events (AMI and stroke) among patients with hyperlipidemia and/or type 2 diabetes. Research to assess interventions to improve adherence to colesevelam and subsequently to evaluate the effects of these interventions on cardiovascular outcomes is warranted. HubMed – drug


Efficient calculation of compound similarity based on maximum common subgraphs and its application to prediction of gene transcript levels.

Int J Bioinform Res Appl. 2013 Jan 1; 9(4): 407-432
Berlo RJ, Winterbach W, Groot MJ, Bender A, Verheijen PJ, Reinders MJ, Ridder DD

Properties of a chemical entity, both physical and biological, are related to its structure. Since compound similarity can be used to infer properties of novel compounds, in chemoinformatics much attention has been paid to ways of calculating structural similarity. A useful metric to capture the structural similarity between compounds is the relative size of the Maximum Common Subgraph (MCS). The MCS is the largest substructure present in a pair of compounds, when represented as graphs. However, in practice it is difficult to employ such a metric, since calculation of the MCS becomes computationally intractable when it is large. We propose a novel algorithm that significantly reduces computation time for finding large MCSs, compared to a number of state-of-the-art approaches. The use of this algorithm is demonstrated in an application predicting the transcriptional response of breast cancer cell lines to different drug-like compounds, at a scale which is challenging for the most efficient MCS-algorithms to date. In this application 714 compounds were compared. HubMed – drug


Use of case-time-control design in pharmacovigilance applications: exploration with high-risk medications and unplanned hospital admissions in the Western Australian elderly.

Pharmacoepidemiol Drug Saf. 2013 Jun 25;
Price SD, Holman CD, Sanfilippo FM, Emery JD

To use a case-time-control design to derive preliminary estimates of unplanned hospitalisations attributable to suspected high-risk medications in elderly Western Australians.Using pharmaceutical claims linked to inpatient and other health records, the study applied a case-time-control design and conditional logistic regression to estimate odds ratios (ORs) for unplanned hospital admissions associated with anticoagulants, antirheumatics, opioids, corticosteroids and four major groups of cardiovascular drugs. Attributable fractions (AFs) were derived from the ORs to estimate the number and proportion of admissions associated with drug exposure. Results were compared with those obtained from a more conventional method using International Classification of Diseases (ICD) external cause codes to identify admissions related to adverse drug events.The study involved 1?899?699 index hospital admissions. Six of the eight drug groups were associated with an increased risk of unplanned hospitalisation, opioids (adjusted OR?=?1.81, 95%CI 1.75-1.88; AF?=?44.9%) and corticosteroids (1.48, 1.42-1.54; 32.2%) linked with the highest risks. For all six, the estimated number of hospitalisations attributed to the medication in the exposed was higher (two to 31-fold) when derived from the case-time-control design compared with identification from ICD codes.This study provides an alternative approach for identifying potentially harmful medications and suggests that the use of ICD external causes may underestimate adverse drug events. It takes drug exposure into account, can be applied to individual medications and may overcome under-reporting issues associated with conventional methods. The approach shows great potential as part of a post-marketing pharmacovigilance monitoring system in Australia and elsewhere. Copyright © 2013 John Wiley & Sons, Ltd. HubMed – drug


Effects of Mitiglinide, a Short-Acting Insulin Secretagogue, on Daily Glycemic Variability and Oxidative Stress Markers in Japanese Patients with Type 2 Diabetes Mellitus.

Clin Drug Investig. 2013 Jun 25;
Kodani N, Saisho Y, Tanaka K, Kawai T, Itoh H

The objective of this study was to clarify the effects of mitiglinide on daily glycemic variability and oxidative stress markers in outpatients with type 2 diabetes mellitus that is insufficiently controlled by diet and/or non-insulin secretagogues.We enrolled 24 patients with type 2 diabetes whose glycemic control had been suboptimal [i.e. glycosylated hemoglobin (HbA1c) ?6.9 %]. The patients were treated with mitiglinide 10 mg three times daily for 16 weeks. If their glycemic control was not improved at week 8, the dose of mitiglinide was increased to 20 mg three times daily. Daily glycemic variability was assessed by 7-point self-monitoring of blood glucose for 2 days, and standard deviation (SD), M value, and mean of daily differences (MODD) were calculated. Oxidative stress was assessed by oxidized low-density lipoprotein, pentosidine, urinary 8-iso-prostaglandin F2alpha, and urinary 8-hydroxydeoxy guanosine.After 16 weeks of mitiglinide treatment, the HbA1c level was significantly decreased (mean ± SD, 7.4 ± 0.7 to 6.8 ± 0.5 %, P < 0.0001). Postprandial glucose excursion and glycemic variability were also significantly improved after mitiglinide treatment (all P < 0.05). The reductions in SD, M value, and MODD were 17, 50, and 48 %, respectively. There was a significant positive correlation between the change in HbA1c and change in SD during the study (r = 0.454, P = 0.03). There were no significant changes in oxidative stress markers.The present study supports the notion that mitiglinide improves postprandial glucose excursion and HbA1c level in patients with type 2 diabetes. In addition, we demonstrated that mitiglinide also effectively improves daily glycemic variability. The effect of mitiglinide on oxidative stress needs further investigation. HubMed – drug