Sukhyang Lee

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.

Evaluation of a computer-based adverse-drug-event monitor

PURPOSE The performance of a computer-based adverse-drug-event (ADE) monitor is evaluated, and the characteristics of ADEs detected and undetected by the monitor are compared. METHODS A retrospective analysis was conducted to identify ADEs using pre-defined ADE alerts that were recognized by a computer-based ADE monitor in a 1300-bed, tertiary care, teaching hospital in Seoul, Korea. A subsequent chart review was conducted by a pharmacist to confirm the ADEs and identify ADEs unrecognized by the monitor. The performance of the monitor was evaluated for its sensitivity and positive predictive value in detecting an ADE. The differences in characteristics of ADEs were compared between computer-recognized ADEs and computer-unrecognized ADEs for severity, causality, preventability, associated clinical manifestations, and types of ADEs. RESULTS During a one-month period, a total of 598 patients from two intensive care units and five general wards were monitored to identify ADEs. The computer-based ADE monitor identified 148 ADEs, and the chart review identified 39 computer-unrecognized ADEs. The sensitivity of the computer-based ADE monitor was 79% (148 of 187). The computer-recognized ADEs were more severe than computer-unrecognized ADEs, but there were no statistically significant differences in the causality, preventability, and types of ADEs. The positive predictive value of the computer monitor was 21% (148 of 718). CONCLUSION The computer-based ADE monitor successfully identified most of the ADEs and almost all of the severe ADEs that occurred in the hospitalized patients. However, the accuracy of the computer-based ADE monitor needs to be improved.

Spontaneously reported hepatic adverse drug events in Korea: multicenter study.

Hepatic adverse drug reactions (ADRs) to certain drugs may differ within each country, reflecting different patterns of prescription, socioeconomic status, and culture. The purpose of this study was to assess the suspected cause of hepatic ADRs using the spontaneously reported pharmacovigilance data from Korea. A total of 9,360 spontaneously reported adverse drug events (ADEs) from nine Pharmacovigilance Centers were analyzed. Risk of hepatic ADEs was assessed by calculating the reporting odds ratio (ROR). Of the 9,360 cases, 567 hepatic ADEs were reported. The most frequently prescribed drug classes inducing hepatic ADEs were anti-tuberculotics, cephalosporins, valproic acids, penicillins, quinolones, non-steroidal anti-inflammatory drugs (NSAIDs), anti-viral agents, and statins. ROR values were especially high in anti-tuberculosis drugs, systemic antifungal drugs for systemic use, anti-epileptics, propylthiouracil, and herbal medicines. Underlying diseases such as tuberculosis (6.9% vs 0.9%), pneumonia (4.9% vs 1.7%), intracranial injury including skull fracture (4.5% vs 0.9%), HIV (3.4% vs 0.4%), subarachnoid hemorrhage (2.8% vs 0.5%), and osteoporosis (2.4% vs 1.4%) were significantly more common in hepatic ADE group. In conclusion, anti-infective drugs, anti-epileptics, NSAIDs and statins are the most common suspects of the spontaneously reported hepatic ADEs, in Korea. Careful monitoring for such reactions is needed for the prescription of these drugs.

Development of a List of Potentially Inappropriate Drugs for the Korean Elderly Using the Delphi Method

Objectives This study aimed to develop a list of potentially inappropriate drugs for the elderly in Korea using the Delphi technique. Methods A Delphi evaluation with a two-round survey was used to reach a consensus on the criteria for inappropriate medications for the elderly in an outpatient setting. The expert panel consisted of 7 family medicine specialists, 3 psychiatrists, 1 neurologist and 3 clinical pharmacists. The level of inappropriateness was determined by considering clinical importance of the risk and availability of alternative therapy, and was rated on a scale of 1 (very low) to 4 (very high). The drugs were categorized into three groups. The first group (Group 1) was drugs that should be avoided. The second (Group 2) was for drugs that need to be monitored. And the third (Group 3) was for drugs with a low level of risk. Results We took a list of 60 ingredients for drugs and created a list of 57 potentially inappropriate ingredients for the elderly, independent of diagnosis. Forty-two drugs were classified as Group 1. 13 drugs were classified as Group 2. And 2 drugs were classified as Group 3. Ninety-three drugs were potentially inappropriate for the elderly with 29 diagnoses. Groups 1, 2, and 3 included 63, 28, and 3 drugs, respectively. Conclusions This study is an important development of a list of drugs potentially inappropriate for the elderly in Korea. The application of this list may be useful for identifying potentially inappropriate medication uses and decreasing drug-related problems.

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.

CYP2C19 polymorphism in Korean patients on warfarin therapy.

This study was designed to assess the effect of CYP2C19 polymorphism on warfarin dosage requirements and bleeding complications in the Korean population. Patients were placed into one of four groups according to the dose of warfarin they received and the presence of bleeding complications: regular dose control, regular dose bleeding, low dose control, and low dose bleeding. Genotyping for CYP2C19*2 and CYP2C19*3 was performed by the restriction fragment length polymorphism method for each patient and each study group. The measured internal normalized ratio (INR) in each dose group was similar even though the administered dosage was significantly different. A total of 66 patients were evaluated for CYP2C19 polymorphism. Among them 25 patients (37.9%) were homozygous wild type. Four patients (6.1%) had heterozygous mutations at both loci. Others had mutations on either the CYP2C19*2 or *3 locus. Higher genetic variation was observed in CYP2C19*2 than in CYP2C19*3 among Korean patients on warfarin therapy. Our data suggested that there is a higher incidence of bleeding complications in patients who have a higher allele frequency of CYP2C19. It was also revealed that the distribution of CYP2C19 polymorphism among Asian populations is more similar than of the distribution among Caucasian populations.

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.

Comparison of hyperkalemic risk in hospitalized patients treated with different angiotensin receptor blockers: a retrospective cohort study using a Korean clinical research database.

BACKGROUND AND AIM Clinical 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. METHODS We 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. RESULTS We 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. CONCLUSION The 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.

Statins and risk for new-onset diabetes mellitus: A real-world cohort study using a clinical research database.

AbstractAlthough concern regarding the increased risk for new-onset diabetes mellitus (NODM) after statin treatment has been raised, there has been a lack of evidence in real-world clinical practice, particularly in East Asians. We investigated whether statin use is associated with risk for NODM in Koreans. We conducted a retrospective cohort study using the clinical research database from electronic health records. The study cohort consisted of 8265 statin-exposed and 33,060 matched nonexposed patients between January 1996 and August 2013. Matching at a 1:4 ratio was performed using a propensity score based on age, gender, baseline glucose levels (mg/dL), and hypertension. The comparative risks for NODM with various statins (atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin) were estimated by both statin exposure versus matched nonexposed and within-class comparisons. The incidence of NODM among the statin-exposed group (6.000 per 1000 patient-years [PY]) was higher than that of the nonexposed group (3.244 per 1000 PY). The hazard ratio (HR) of NODM after statin exposure was 1.872 (95% confidence interval [CI], 1.432–2.445). Male gender (HR, 1.944; 95% CI, 1.497–2.523), baseline glucose per mg/dL (HR, 1.014; 95% CI, 1.013–1.016), hypertension (HR, 2.232; 95% CI, 1.515–3.288), and thiazide use (HR, 1.337; 95% CI, 1.081–1.655) showed an increased risk for NODM, while angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker showed a decreased risk (HR, 0.774; 95% CI, 0.668–0.897). Atorvastatin-exposed patients showed a higher risk for NODM than their matched nonexposed counterparts (HR, 1.939; 95% CI, 1.278–2.943). However, the risk for NODM was not significantly different among statins in within-class comparisons. In conclusion, an increased risk for NODM was observed among statin users in a practical healthcare setting in Korea.

Specific gas chromatographic analysis of diethylcarbamazine in human plasma using solid-phase extraction.

Diethylcarbamazine (DEC, 1-diethylcarbamyl-4-methylpiperazine) is an antiparasitic piperazine derivative used in the treatment of lymphatic filariasis. DEC-N-oxide is a major metabolite in humans which has antifilarial activity. Gas chromatographic analysis of DEC in plasma can be complicated by the presence of the metabolite, since the thermally unstable DEC-N-oxide is converted to a material which coelutes with DEC under the conditions of the analysis. We now report a method to separate DEC-N-oxide from DEC in plasma using solid-phase extraction with subsequent gas chromatographic analysis using a nitrogen specific detector. 1-Diethylcarbamyl-4-ethylpiperazine (E-DEC) was the internal standard. The standard curve of DEC is linear in the range of 10 to 200 ng/ml. The limit of detection is 4 ng/ml. Reproducibility at 10, 100 and 200 ng/ml concentration points of the standard curve gives coefficients of variation of 6.1%, 7.8% and 1.6%, respectively. Recovery following solid-phase extraction is 99.3% for DEC and 94.8% for the internal standard. This sensitive and specific analytical method is suitable for pharmacokinetic studies of DEC.