Dukyong Yoon

Detection of adverse drug reaction signals using an electronic health records database: Comparison of the Laboratory Extreme Abnormality Ratio (CLEAR) algorithm.

Electronic health records (EHRs) are expected to be a good source of data for pharmacovigilance. However, current quantitative methods are not applicable to EHR data. We propose a novel quantitative postmarketing surveillance algorithm, the Comparison of Laboratory Extreme Abnormality Ratio (CLEAR), for detecting adverse drug reaction (ADR) signals from EHR data. The methodology involves calculating the odds ratio of laboratory abnormalities between a specific drug‐exposed group and a matched unexposed group. Using a 10‐year EHR data set, we applied the algorithm to test 470 randomly selected drug–event pairs. It was found possible to analyze a single drug–event pair in just 109 ± 159 seconds. In total, 120 of the 150 detected signals corresponded with previously reported ADRs (positive predictive value (PPV) = 0.837 ± 0.113, negative predictive value (NPV) = 0.659 ± 0.180). By quickly and efficiently identifying ADR signals from EHR data, the CLEAR algorithm can significantly contribute to the utilization of EHR data for pharmacovigilance.

A novel algorithm for detection of adverse drug reaction signals using a hospital electronic medical record database

Quantitative analytic methods are being increasingly used in postmarketing surveillance. However, currently existing methods are limited to spontaneous reporting data and are inapplicable to hospital electronic medical record (EMR) data. The principal objectives of this study were to propose a novel algorithm for detecting the signals of adverse drug reactions using EMR data focused on laboratory abnormalities after treatment with medication, and to evaluate the potential use of this method as a signal detection tool.

Is there any correlation between model-based perfusion parameters and model-free parameters of time-signal intensity curve on dynamic contrast enhanced MRI in breast cancer patients?

ObjectiveTo find out any correlation between dynamic contrast-enhanced (DCE) model-based parameters and model-free parameters, and evaluate correlations between perfusion parameters with histologic prognostic factors.MethodsModel-based parameters (Ktrans, Kep and Ve) of 102 invasive ductal carcinomas were obtained using DCE-MRI and post-processing software. Correlations between model-based and model-free parameters and between perfusion parameters and histologic prognostic factors were analysed.ResultsMean Kep was significantly higher in cancers showing initial rapid enhancement (P = 0.002) and a delayed washout pattern (P = 0.001). Ve was significantly lower in cancers showing a delayed washout pattern (P = 0.015). Kep significantly correlated with time to peak enhancement (TTP) (ρ = −0.33, P < 0.001) and washout slope (ρ = 0.39, P = 0.002). Ve was significantly correlated with TTP (ρ = 0.33, P = 0.002). Mean Kep was higher in tumours with high nuclear grade (P = 0.017). Mean Ve was lower in tumours with high histologic grade (P = 0.005) and in tumours with negative oestrogen receptor status (P = 0.047). TTP was shorter in tumours with negative oestrogen receptor status (P = 0.037).ConclusionsWe could acquire general information about the tumour vascular physiology, interstitial space volume and pathologic prognostic factors by analyzing time-signal intensity curve without a complicated acquisition process for the model-based parameters.Key points• Kep mainly affected the initial and delayed curve pattern in time–signal intensity curve.• There is significant correlation between model-based and model-free parameters.• We acquired information about tumour vascular physiology, interstitial space volume and prognostic factors.

Dipeptidyl Peptidase-4 Inhibitors and Risk of Heart Failure in Patients With Type 2 Diabetes Mellitus: A Population-Based Cohort Study

Background: The association between dipeptidyl-peptidase IV inhibitors (DPP-4i) and heart failure (HF) remains unclear. In 1 randomized controlled trial and some observational studies, DPP-4i reportedly increased the risk of HF, but 2 other randomized controlled trials and observational studies have shown no such risk. Here, we evaluated the risk of HF and cardiovascular outcomes of DPP-4i compared with sulfonylureas. Methods and Results: A population-based retrospective cohort study was conducted using the Korean Health Insurance Review and Assessment Service database from January 1, 2009, to December 31, 2015. Incident users of sulfonylurea and DPP-4i who were not prescribed the comparator drug in the year before treatment initiation were included. DPP-4i–treated and sulfonylurea-treated patients were matched on propensity score, calculated with >40 variables. The risk of hospitalization for HF was evaluated with a Cox proportional hazards model in 255 691 matched pairs. Analyses were conducted in the total patient population and in both strata divided by the presence of cardiovascular disease during the baseline period. The hazard ratios (HRs) of hospitalization for HF for DPP-4i–treated patients were 0.78 (95% confidence interval [CI], 0.67–0.86) in all of the patients, 0.77 (95% CI, 0.68–0.79) in patients with baseline cardiovascular disease, and 0.71 (95% CI, 0.56–0.90) in patients without baseline cardiovascular disease compared with HRs for sulfonylurea-treated patients. Sitagliptin and linagliptin showed statistically lower risk for hospitalization for HF (HR, 0.76; 95% CI, 0.67–0.86 for sitagliptin-prescribed patients; HR, 0.74; 95% CI, 0.59–0.92 for linagliptin-prescribed patients) than for sulfonylurea. The HRs for hospitalization for myocardial infarction and stroke with the use of a DPP-4i versus sulfonylurea were HR, 0.76 (95% CI, 0.67–0.87) and HR, 0.63 (95% CI, 0.60–0.67), respectively. Conclusions: Our findings suggest that DPP-4i use did not increase the risk of HF compared with sulfonylurea. In addition, the risks for cardiovascular outcomes were not elevated in DPP-4i–treated patients compared with sulfonylurea-treated patients.

The relationship between the failure to eradicate Helicobacter pylori and previous antibiotics use.

BACKGROUND The previous use of antibiotics is known to correlate positively with antibiotic resistance; whether this is also the case in the eradication of Helicobacter pylori infection is unclear. AIM To investigate the relationship between the previous use of antibiotics and the failure of eradication therapy in H. pylori infection. METHODS The relationship between the clinical parameters and the failure of H. pylori eradication was analyzed in patients administered standard triple therapy and then assessed for the eradication of H. pylori based on a C13-urea breath test. RESULTS In a multivariate analysis, failure rates increased significantly in patients with a history of clarithromycin (odds ratio [OR], 4.445) or other macrolides (OR, 2.407) use, who were female (OR, 1.339), or who were older than 60 years of age (OR, 1.326). The eradication failure rate in patients with a history of macrolides use for >2 weeks was significantly higher than if the duration of use was <2 weeks (44.8% vs. 29.3%, p=0.047). CONCLUSIONS A patients history of macrolides is a useful predictor of the likelihood of standard triple therapy failure in H. pylori eradication. The alternatives such as a bismuth-based quadruple or a levofloxacin-containing therapy should be considered in patients treated with macrolides for >2 weeks.

Construction of an Open-Access QT Database for Detecting the Proarrhythmia Potential of Marketed Drugs: ECG-ViEW

Information about the QT interval from surface electrocardiograms (ECGs) is essential for surveillance of the proarrhythmia potential of marketed drugs. However, ECG records obtained in daily practice cannot be easily used for this purpose without labor‐intensive manual effort. This study was aimed at constructing an open‐access QT database, the Electrocardiogram Vigilance with Electronic Data Warehouse (ECG‐ViEW). This longitudinal observational database contains 710,369 measurements of QT and associated clinical data from 371,401 patients. The de‐identified database is freely available at http://www.ecgview.org.

Onset time of hyperkalaemia after angiotensin receptor blocker initiation: when should we start serum potassium monitoring?

Angiotensin receptor blockers (ARBs) frequently induce hyperkalaemia in high‐risk patients. Early detection of hyperkalaemia can reduce the subsequent harmful effects. This study was performed to examine the onset time of hyperkalaemia after ARB therapy.

Integrative analysis of congenital muscular torticollis: from gene expression to clinical significance

BackgroundCongenital muscular torticollis (CMT) is characterized by thickening and/or tightness of the unilateral sternocleidomastoid muscle (SCM), ending up with torticollis. Our aim was to identify differentially expressed genes (DEGs) and novel protein interaction network modules of CMT, and to discover the relationship between gene expressions and clinical severity of CMT.ResultsTwenty-eight sternocleidomastoid muscles (SCMs) from 23 subjects with CMT and 5 SCMs without CMT were allocated for microarray, MRI, or imunohistochemical studies. We first identified 269 genes as the DEGs in CMT. Gene ontology enrichment analysis revealed that the main function of the DEGs is for extracellular region part during developmental processes. Five CMT-related protein network modules were identified, which showed that the important pathway is fibrosis related with collagen and elastin fibrillogenesis with an evidence of DNA repair mechanism. Interestingly, the expression levels of the 8 DEGs called CMT signature genes whose mRNA expression was double-confirmed by quantitative real time PCR showed good correlation with the severity of CMT which was measured with the pre-operational MRI images (R2 ranging from 0.82 to 0.21). Moreover, the protein expressions of ELN, ASPN and CHD3 which were identified from the CMT-related protein network modules demonstrated the differential expression between the CMT and normal SCM.ConclusionsWe here provided an integrative analysis of CMT from gene expression to clinical significance, which showed good correlation with clinical severity of CMT. Furthermore, the CMT-related protein network modules were identified, which provided more in-depth understanding of pathophysiology of CMT.

Renal Protective Effect of DPP-4 Inhibitors in Type 2 Diabetes Mellitus Patients: A Cohort Study.

Aims. Dipeptidyl-peptidase IV inhibitors (DPP-4i) are among the most popular oral antidiabetic agents. However, the effects of DPP-4i on diabetic nephropathy are not well-established. The aim of this study was to determine the renoprotective effects of DPP-4i, using albuminuria and glomerular filtration rate (GFR) as indicators, in type 2 diabetes mellitus (T2DM) patients. Methods. This retrospective observational cohort study used the clinical database of a tertiary hospital. The changes of urine albumin/creatinine ratio (UACR), estimated GFR (eGFR), and metabolic parameters after treatment were compared with the changes of those parameters before treatment using paired Students t-test. Results. The mean UACR in the entire study population decreased to approximately 45 mg/g 1 year after DPP-4i treatment, while it was increased approximately 39 mg/g 1 year before DPP-4i treatment (p < 0.05). Patients with macroalbuminuria showed a significant reduction in albumin levels after DPP-4i treatment (p < 0.05); however, patients with microalbuminuria and normoalbuminuria did not show improvements in albuminuria levels after treatment. Although eGFR was not changed 1 year after DPP-4i treatment, reductions in eGFR were slowed in patients with microalbuminuria and reversed in the macroalbuminuria or normoalbuminuria groups, 4 years after treatment. Conclusions. Administration of DPP-4i reduces urine albumin excretion and mitigates reduction of eGFR in T2DM patients.

Comparison of Hyperkalemic Risk in Hospitalized Patients Treated with Different Angiotensin Receptor Blockers

Background and AimClinical use of angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) is associated with hyperkalemia as an adverse drug reaction. Although it has significant clinical implications, the incidence and relative risks of hyperkalemia with various ARBs have not yet been fully evaluated. The purpose of this study was to determine the risk of hyperkalemic events in hospitalized patients treated with different ARBs and to compare the risk among them.MethodsWe constructed a retrospective cohort composed of hospitalized adult patients who took ARBs in a single tertiary teaching hospital between April 2004 and March 2010. We estimated the incidence of hyperkalemia (serum potassium level >5.5 mEq/L) with various ARBs, and then compared the risk between them using a multivariate Cox proportional hazard model based on age, sex, Charlson co-morbidity score, baseline serum potassium, underlying diseases, and concomitant drugs.ResultsWe identified 6992 evaluable intervals from 5449 patients treated with one of the seven ARBs during hospitalization over the 71-month study period with 2521.6 patient-months. We found 381 hyperkalemic events (5.4%) during the study period and an overall event rate of 15.1/100 patient-months. Moderate to fatal hyperkalemia was relatively rare (>6.0 mEq/L, 2.1% [moderate]; >6.5 mEq/L, 0.9% [severe]; >7.0 mEq/L, 0.3% [fatal]). After adjustment for covariates, telmisartan showed a lower risk of hyperkalemia (hazard ratio 0.67; 95% confidence interval 0.51, 0.89) compared with all other ARBs.ConclusionThe risk of hyperkalemic events in hospitalized patients treated with different ARBs was defined. Telmisartan showed a relatively lower hyperkalemic risk profile in hospitalized patients compared with other ARBs.