Cheng Yang Hsieh

Terminating prolonged refractory status epilepticus using ketamine.

Refractory status epilepticus (RSE) is an emergent and difficult neurologic problem that is not uncommon in clinical practice. In this report, we describe a 23-year-old man whose RSE was refractory to standard antiepileptic drugs and barbiturates; it was successfully terminated only with intravenous ketamine. In this report, we evaluated and discuss the clinical and electroencephalographic effects under ketamine. This case and the rare cases of ketamine experience in RSE reported in the literature show that ketamine is potentially effective to use when treating patients with RSE. Further clinical trials are warranted, however.

Developing a stroke severity index based on administrative data was feasible using data mining techniques

OBJECTIVES Case-mix adjustment is difficult for stroke outcome studies using administrative data. However, relevant prescription, laboratory, procedure, and service claims might be surrogates for stroke severity. This study proposes a method for developing a stroke severity index (SSI) by using administrative data. STUDY DESIGN AND SETTING We identified 3,577 patients with acute ischemic stroke from a hospital-based registry and analyzed claims data with plenty of features. Stroke severity was measured using the National Institutes of Health Stroke Scale (NIHSS). We used two data mining methods and conventional multiple linear regression (MLR) to develop prediction models, comparing the model performance according to the Pearson correlation coefficient between the SSI and the NIHSS. We validated these models in four independent cohorts by using hospital-based registry data linked to a nationwide administrative database. RESULTS We identified seven predictive features and developed three models. The k-nearest neighbor model (correlation coefficient, 0.743; 95% confidence interval: 0.737, 0.749) performed slightly better than the MLR model (0.742; 0.736, 0.747), followed by the regression tree model (0.737; 0.731, 0.742). In the validation cohorts, the correlation coefficients were between 0.677 and 0.725 for all three models. CONCLUSION The claims-based SSI enables adjusting for disease severity in stroke studies using administrative data.

Validation of algorithms to identify stroke risk factors in patients with acute ischemic stroke, transient ischemic attack, or intracerebral hemorrhage in an administrative claims database.

BACKGROUND Stroke patients have a high risk for recurrence, which is positively correlated with the number of risk factors. The assessment of risk factors is essential in both stroke outcomes research and the surveillance of stroke burden. However, methods for assessment of risk factors using claims data are not well developed. METHODS We enrolled 6469 patients with acute ischemic stroke, transient ischemic attack, or intracerebral hemorrhage from hospital-based stroke registries, which were linked with Taiwans National Health Insurance (NHI) claims database. We developed algorithms using diagnosis codes and prescription data to identify stroke risk factors including hypertension, diabetes, hyperlipidemia, atrial fibrillation (AF), and coronary artery disease (CAD) in the claims database using registry data as reference standard. We estimated the kappa statistics to quantify the agreement of information on the risk factors between claims and registry data. RESULTS The prevalence of risk factors in the registries was hypertension 77.0%, diabetes 39.1%, hyperlipidemia 55.6%, AF 10.1%, and CAD 10.9%. The highest kappa statistics were 0.552 (95% confidence interval 0.528-0.577) for hypertension, 0.861 (0.836-0.885) for diabetes, 0.572 (0.549-0.596) for hyperlipidemia, 0.687 (0.663-0.712) for AF, and 0.480 (0.455-0.504) for CAD. Algorithms based on diagnosis codes alone could achieve moderate to high agreement in identifying the selected risk factors, whereas prescription data helped improve identification of hyperlipidemia. CONCLUSIONS We tested various claims-based algorithms to ascertain important risk factors in stroke patients. These validated algorithms are useful for assessing stroke risk factors in future studies using Taiwans NHI claims data.

Comparative stroke risk of antiepileptic drugs in patients with epilepsy

Purpose:  Patients with epilepsy have higher stroke‐related morbidity and mortality, leading to the suspicion that the increased stroke events may be associated with antiepileptic drug (AED) exposure. We evaluated the comparative risk of stroke in adult patients with epilepsy receiving phenytoin (PHT), valproic acid (VPA), or carbamazepine (CBZ) to help determine the stroke risk for Asian patients with specific AED exposure.

Use of antiepileptic drugs and risk of hypothyroidism

This study aimed to investigate the risk of clinically significant hypothyroidism among all the currently available antiepileptic drugs (AED).

Outcome of Acute Ischemic Stroke in Very Elderly Patients: Is Intravenous Thrombolysis Beneficial?

Background/Aims: Intravenous tissue plasminogen activator (tPA) treatment is recommended in acute stroke within 3 h of onset; however, the benefit of its use in the elderly remains uncertain. We assessed the safety and efficacy of tPA treatment in elderly patients. Methods: We recruited 97 elderly Chinese patients aged ≧80 years with cerebral ischemia presenting within 3 h of onset. Favorable outcomes were defined as discharge to home and modified Rankin Scale (mRS) ≤2 at discharge. Results: For moderate to severe patients (NIHSS ≧6), the baseline characteristics between the tPA (n = 30) and non-tPA (n = 41) group were not different. The proportion of patients discharged home was 56.7 and 61%, respectively (p = 0.72). For patients with baseline mRS ≤2, the frequency of discharged mRS ≤2 was not different (27.3% of the tPA group and 26.9% of the non-tPA group; p = 1.00). Symptomatic intracranial hemorrhage was 6.7 and 2.4%, respectively (p = 0.31). For minor stroke patients (NIHSS ≤5), tPA was not considered and the outcome of those discharged home and mRS ≤2 was 73 and 88%, respectively. Conclusion: Elderly patients can be treated safely with intravenous tPA, whereas our data did not support routine thrombolysis. Further randomized trials in the elderly are encouraged.

Rhabdomyolysis and pancreatitis associated with coadministration of danazol 600 mg/d and lovastatin 40 mg/d

BACKGROUND Danazol is a steroid analogue with anabolic and androgenic effects and is indicated for the treatment of endometriosis, fibrocystic diseases of the breast, and hereditary angioedema. Lovastatin has been prescribed to lower total cholesterol and low-density lipoprotein cholesterol, reducing cardiovascular-related morbidity and mortality in patients with hypercholesterolemia. As monotherapies, both danazol and lovastatin have been reported to induce myopathy and pancreatitis. CASE SUMMARY A 59-year-old Asian woman (height, 155 cm; weight, 54 kg; and body mass index, 22.5 kg/m2) presented to the outpatient neurology clinic with acute progressive quadriparesis and generalized myalgia (without focal sensory loss, numbness, dizziness, diplopia, dysarthria, dysphagia, or sphincter incontinence), lasting for 5 days. She was admitted to the National Cheng Kung University Hospital, Tainan, Taiwan. The patients medical history revealed multiple comorbidities (eg, end-stage renal disease, hypertension, diabetes mellitus) for which she was receiving concomitant medication. Her medication history revealed that at the time the patient presented, she was also receiving calcium bicarbonate 1500 mg/d, labetalol 100 mg/d, and glipizide 10 mg/d in the treatment of her other comorbid illnesses. The patient was also receiving alprazolam 0.5 mg/d for insomnia. Her medical records also revealed that lovastatin 40 mg/d (a particularly high dose and not recommended) had been administered for 7 weeks, and danazol 600 mg/d was added ( approximately 15 days later) to treat thrombocytopenia due to hypoplastic bone marrow. Laboratory findings revealed elevated creatine kinase (68,193 U/L), elevated pancreatic enzymes (amylase/lipase, 361/2788 U/L), and elevated liver enzymes (aspartate/alanine aminotransferase, 1496/1493 U/L), consistent with rhabdomyolysis and pancreatitis. After discontinuation of both drugs, the symptoms improved 5 days after admission and completely disappeared 1 month after admission. In addition, laboratory abnormalities completely normalized approximately 2 months after admission. Danazol was resumed to treat persistent thrombocytopenia, while lovastatin was replaced with ezetimibe 10 mg QD to treat high cholesterol (dyslipidemia). CONCLUSION The coadministration of high-dose lovastatin and danazol was probably associated with rhabdomyolysis and pancreatitis in this patient with multiple underlying comorbidities for which concomitant medications were being administered.

Sequence symmetry analysis in pharmacovigilance and pharmacoepidemiologic studies

Sequence symmetry analysis (SSA) is a method for detecting adverse drug events by utilizing computerized claims data. The method has been increasingly used to investigate safety concerns of medications and as a pharmacovigilance tool to identify unsuspected side effects. Validation studies have indicated that SSA has moderate sensitivity and high specificity and has robust performance. In this review we present the conceptual framework of SSA and discuss advantages and potential pitfalls of the method in practice. SSA is based on analyzing the sequences of medications; if one medication (drug B) is more often initiated after another medication (drug A) than before, it may be an indication of an adverse effect of drug A. The main advantage of the method is that it requires a minimal dataset and is computationally efficient. By design, SSA controls time-constant confounders. However, the validity of SSA may be affected by time-varying confounders, as well as by time trends in the occurrence of exposure or outcome events. Trend effects may be adjusted by modeling the expected sequence ratio in the absence of a true association. There is a potential for false positive or negative results and careful consideration should be given to potential sources of bias when interpreting the results of SSA studies.

Net Clinical Benefit of Oral Anticoagulants: A Multiple Criteria Decision Analysis

Background This study quantitatively evaluated the comparative efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, and apizaban) and warfarin for treatment of nonvalvular atrial fibrillation. We also compared these agents under different scenarios, including population with high risk of stroke and for primary vs. secondary stroke prevention. Methods We used multiple criteria decision analysis (MCDA) to assess the benefit-risk of these medications. Our MCDA models contained criteria for benefits (prevention of ischemic stroke and systemic embolism) and risks (intracranial and extracranial bleeding). We calculated a performance score for each drug accounting for benefits and risks in comparison to treatment alternatives. Results Overall, new agents had higher performance scores than warfarin; in order of performance scores: dabigatran 150 mg (0.529), rivaroxaban (0.462), apixaban (0.426), and warfarin (0.191). For patients at a higher risk of stroke (CHADS2 score≥3), apixaban had the highest performance score (0.686); performance scores for other drugs were 0.462 for dabigatran 150 mg, 0.392 for dabigatran 110 mg, 0.271 for rivaroxaban, and 0.116 for warfarin. Dabigatran 150 mg had the highest performance score for primary stroke prevention, while dabigatran 110 mg had the highest performance score for secondary prevention. Conclusions Our results suggest that new oral anticoagulants might be preferred over warfarin. Selecting appropriate medicines according to the patient’s condition based on information from an integrated benefit-risk assessment of treatment options is crucial to achieve optimal clinical outcomes.

Databases in the Asia-pacific region: The potential for a distributed network approach

Background: This study describes the availability and characteristics of databases in Asian-Pacific countries and assesses the feasibility of a distributed network approach in the region. Methods: A web-based survey was conducted among investigators using healthcare databases in the Asia-Pacific countries. Potential survey participants were identified through the Asian Pharmacoepidemiology Network. Results: Investigators from a total of 11 databases participated in the survey. Database sources included four nationwide claims databases from Japan, South Korea, and Taiwan; two nationwide electronic health records from Hong Kong and Singapore; a regional electronic health record from western China; two electronic health records from Thailand; and cancer and stroke registries from Taiwan. Conclusions: We identified 11 databases with capabilities for distributed network approaches. Many country-specific coding systems and terminologies have been already converted to international coding systems. The harmonization of health expenditure data is a major obstacle for future investigations attempting to evaluate issues related to medical costs.