High Neutrophil-to-Lymphocyte Ratio Predicts One-Year Risk of Pneumonia Post-Stroke Discharge.

INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) may predict stroke-associated pneumonia, which is generally defined as pneumonia occurring in the first week after stroke. However, little is known whether the initial NLR is associated with pneumonia risk during the long-term follow-up in stroke survivors. We aimed to determine the relationship between admission NLR and the risk of post-stroke pneumonia within 1 year after discharge from acute stroke care. METHODS: Hospital databases were searched to identify adult patients hospitalized for acute stroke. Admission NLR was extracted using differential leukocyte counts. The outcome of interest was hospitalized pneumonia occurring within 1 year after discharge from hospitalization for stroke. Multivariable Cox proportional-hazards models were used to determine the independent effects of the NLR on the risk of pneumonia. RESULTS: In this study, 5,741 patients with acute stroke (mean age, 68 years; men, 62.1%) were analyzed. The median NLR was 2.72 (interquartile range, 1.78-4.49). Of the patients, 342 (6.0%) developed pneumonia within 1 year after discharge. In the multivariable models, the NLR was a significant predictor of pneumonia after discharge whether it was analyzed as a continuous or dichotomized variable. The corresponding adjusted hazard ratios were 1.037 (95% confidence interval [CI], 1.013-1.061) and 1.361 (95% CI, 1.087-1.704), respectively. CONCLUSION: The NLR could predict the risk of post-stroke pneumonia up to 1 year after discharge from acute stroke care. It may help identify high-risk stroke survivors, for whom appropriate interventions can be targeted.

Herpes zoster associated with stroke incidence in people living with human immunodeficiency virus: a nested case-control study.

BACKGROUND: The incidence of stroke is increasing among younger people with human immunodeficiency virus (HIV). The burden of stroke has shifted toward the young people living with HIV, particularly in low- and middle-income countries. People infected with herpes zoster (HZ) were more likely to suffer stroke than the general population. However, the association of HZ infection with the incidence of stroke among patients with HIV remains unclear. METHODS: A nested case-control study was conducted with patients with HIV registered in the Taiwan National Health Insurance Research Database in 2000-2017. A total of 509 stroke cases were 1:10 matched to 5090 non-stroke controls on age, sex, and date of first stroke diagnosis. Logistic regression models were used to estimate the odds ratio and 95% confidence intervals (CI) of stroke incidence. RESULTS: The odds ratio of stroke was significantly higher in the HIV-infected population with HZ (adjusted odds ratio [AOR]: 1.85, 95% CI: 1.42-2.41). A significantly increased AOR of stroke was associated with hypertension (AOR: 3.53, 95% CI: 2.86-4.34), heart disease (AOR: 2.32, 95% CI: 1.54-3.48), chronic kidney disease (AOR: 1.82, 95% CI: 1.16-2.85), hepatitis C virus infection (AOR: 1.49, 95% CI: 1.22-1.83), hyperlipidemia (OR: 1.41, 95% CI: 1.12-1.78), and treatment with protease inhibitors (AOR: 1.33, 95% CI: 1.05-1.69). CONCLUSIONS: Our findings suggest that HZ concurrent with HIV may increase the risk of stroke. The incidence rates of stroke were independent of common risk factors, suggesting strategies for early prevention of HZ infection among people living with HIV.

Incidence, prescription patterns and risk factors of antipsychotic initiation in elderly stroke survivors.

OBJECTIVES: Epidemiological data regarding antipsychotic initiation in elderly patients with stroke are limited. We aimed to investigate the incidence, prescription patterns and determinants of antipsychotic initiation in elderly patients with stroke. METHODS: We conducted a retrospective cohort study to identify patients aged above 65 years who had been admitted for stroke from the National Health Insurance Database (NHID). The index date was defined as the discharge date. The incidence and prescription pattern of antipsychotics were estimated using the NHID. To evaluate the determinants of antipsychotic initiation, the cohort identified from the NHID was linked to the Multicenter Stroke Registry (MSR). Demographics, comorbidities and concomitant medications were obtained from the NHID. Information including smoking status, body mass index, stroke severity and disability was retrieved by linking to the MSR. The outcome was antipsychotic initiation after the index date. Hazard ratios for antipsychotic initiation were estimated using the multivariable Cox model. RESULTS: In terms of prognosis, the first 2 months after a stroke was the highest-risk period for antipsychotic use. A high burden of coexisting diseases carried an increased risk of antipsychotic use; in particular, chronic kidney disease (CKD) had the highest adjusted hazard ratio (aHR = 1.73; 95% CI 1.29-2.31) as compared with other risk factors. Furthermore, stroke severity and disability were significant risk factors for antipsychotic initiation. CONCLUSIONS: Our study indicated that elderly stroke patients with chronic medical conditions, particularly CKD, and a higher stroke severity and disability were at greater risk of psychiatric disorders during the first 2 months after a stroke. CLINICAL TRIAL REGISTRATION: NA.

Interactive deciphering electron-shuttling characteristics of Coffea arabica leaves and potential bioenergy-steered anti-SARS-CoV-2 RdRp inhibitor via microbial fuel cells.

Due to the pandemics of COVID-19, herbal medicine has recently been explored for possible antiviral treatment and prevention via novel platform of microbial fuel cells. It was revealed that Coffea arabica leaves was very appropriate for anti-COVID-19 drug development. Antioxidant and anti-inflammatory tests exhibited the most promising activities for C. arabica ethanol extracts and drying approaches were implemented on the leaf samples prior to ethanol extraction. Ethanol extracts of C. arabica leaves were applied to bioenergy evaluation via DC-MFCs, clearly revealing that air-dried leaves (CA-A-EtOH) exhibited the highest bioenergy-stimulating capabilities (ca. 2.72 fold of power amplification to the blank). Furthermore, molecular docking analysis was implemented to decipher the potential of C. arabica leaves metabolites. Chlorogenic acid (-6.5 kcal/mol) owned the highest binding affinity with RdRp of SARS-CoV-2, showing a much lower average RMSF value than an apoprotein. This study suggested C. arabica leaves as an encouraging medicinal herb against SARS-CoV-2.

In Silico Analysis of Anti-Inflammatory and Antioxidant Properties of Bioactive Compounds from Crescentia cujete L.

Crescentia cujete is widely known as a medical plant with broad indigenous ethnomedicinal uses, including anti-inflammatory, and antioxidant. Despite being used for remedies and ethnomedicinal purposes, the benefits obtained from C. cujete still need to be fully utilized. The underwhelming studies on its pharmacological potential, bioactive compounds, and mechanism of action keep the pharmacological and new drug discovery progress of this plant slow. This study focuses on the incorporation of in silico analyses such as ADME prediction and molecular docking simulations on the bioactive compounds identified in the plant to assess their potential for antioxidant and anti-inflammatory applications. A comparison of the ADME properties and molecular docking scores showed that naringenin, pinocembrin, and eriodictyol had the most potential to act as inhibitors of the target proteins involved in inflammation and oxidation pathways against the positive controls.

Sesamin: A Promising Therapeutic Agent for Ameliorating Symptoms of Diabetes.

Diabetes is a chronic metabolic disease characterized by improperly regulating proteins, carbohydrates, and lipids due to insulin deficiency or resistance. The increasing prevalence of diabetes poses a tremendous socioeconomic burden worldwide, resulting in the rise of many studies on Chinese herbal medicines to discover the most effective cure for diabetes. Sesame seeds are among these Chinese herbal medicines that were found to contain various pharmacological activities, including antioxidant and anti-inflammatory properties, lowering cholesterol, improving liver function, blood pressure and sugar lowering, regulating lipid synthesis, and anticancer activities. These medicinal benefits are attributed to sesamin, which is the main lignan found in sesame seeds and oil. In this study, Wistar rat models were induced with type 2 diabetes using streptozotocin (STZ) and nicotinamide, and the effect of sesamin on the changes in body weight, blood sugar level, glycosylated hemoglobin (HbA1c), insulin levels, and the states of the pancreas and liver of the rats were evaluated. The results indicate a reduced blood glucose level, HbA1c, TG, and ALT and AST enzymes after sesamin treatment, while increased insulin level, SOD, CAT, and GPx activities were also observed. These findings prove sesamin's efficacy in ameliorating the symptoms of diabetes through its potent pharmacological activities.

Atrial Fibrillation Detected After Stroke and Transient Ischemic Attack: A Novel Clinical Concept Challenging Current Views.

Atrial fibrillation (AF) can be newly detected in approximately one-fourth of patients with ischemic stroke and transient ischemic attack without previously recognized AF. We present updated evidence supporting that AF detected after stroke or transient ischemic attack (AFDAS) may be a distinct clinical entity from AF known before stroke occurrence (known atrial fibrillation). Data suggest that AFDAS can arise from the interplay of cardiogenic and neurogenic forces. The embolic risk of AFDAS can be understood as a gradient defined by the prevalence of vascular comorbidities, the burden of AF, neurogenic autonomic changes, and the severity of atrial cardiopathy. The balance of existing data indicates that AFDAS has a lower prevalence of cardiovascular comorbidities, a lower degree of cardiac abnormalities than known atrial fibrillation, a high proportion (52%) of very brief (<30 seconds) AF paroxysms, and is more frequently associated with insular brain infarction. These distinctive features of AFDAS may explain its recently observed lower associated risk of stroke than known atrial fibrillation. We present an updated ad-hoc meta-analysis of randomized clinical trials in which the association between prolonged cardiac monitoring and reduced risk of ischemic stroke was nonsignificant (incidence rate ratio, 0.90 [95% CI, 0.71-1.15]). These findings highlight that larger and sufficiently powered randomized controlled trials of prolonged cardiac monitoring assessing the risk of stroke recurrence are needed. Meanwhile, we call for further research on AFDAS and stroke recurrence, and a tailored approach when using prolonged cardiac monitoring after ischemic stroke or transient ischemic attack, focusing on patients at higher risk of AFDAS and, more importantly, at higher risk of cardiac embolism.

From Kidney Protection to Stroke Prevention: The Potential Role of Sodium Glucose Cotransporter-2 Inhibitors.

Chronic kidney disease (CKD) is an independent risk factor for stroke and covert cerebrovascular disease, and up to 40% of stroke patients have concomitant CKD. However, the so-called "cerebrorenal interaction" attracted less attention compared to its cardiorenal counterpart. Diabetes is the leading cause of CKD. The sodium-glucose cotransporter (SGLT) 2 inhibitor is a relatively new class of oral anti-diabetic drugs and has cardiorenal benefits in addition to glucose-lowering effects. In the present perspective, we would like to review the current status and future potential of the SGLT2 inhibitor in cerebro-renal interactions and strokes regardless of the status of diabetes. We propose the potential roles of baseline renal functions and SGLT1/2 dual inhibition in stroke prevention, as well as the additional benefits of reducing atrial fibrillation and hemorrhagic stroke for SGLT2 inhibitors. Further clinical trials are anticipated to test whether SGLT2 inhibitors can fulfill the long-standing unmet clinical need and stop such a vicious cycle of cerebro-renal interaction.

Association between methylphenidate and risk of myocardial infarction: A multinational self-controlled case series study.

PURPOSE: To investigate the association between use of methylphenidate and risk of myocardial infarction among Asians. METHODS: We conducted a multinational self-controlled case series study using nationwide healthcare databases of South Korea (2002-2018), Taiwan (2004-2015), and Hong Kong (2001-2016). Of patients with myocardial infarction who were also prescribed methylphenidate within the observation period, methylphenidate use was classified into four mutually exclusive periods by each person-day: exposed (exposed to methylphenidate), pre-exposure (prior to the first methylphenidate prescription), washout (after the end of methylphenidate treatment), and baseline (unexposed to methylphenidate). Risk of myocardial infarction among the three periods of methylphenidate use was compared to the baseline period using conditional Poisson regression analysis to estimate incidence rate ratios (IRRs) with 95% confidence intervals (CIs). RESULTS: We identified 2104, 484, and 30 patients from South Korea, Taiwan, and Hong Kong, respectively. Risk of myocardial infarction was the highest during the pre-exposure period in all three populations: South Korea, pre-exposure (IRR 3.17, 95% CI 3.04-3.32), exposed (1.05, 1.00-1.11), washout (1.92, 1.80-2.04); Taiwan, pre-exposure (1.97, 1.78-2.17), exposed (0.72, 0.65-0.80), washout (0.56, 0.46-0.68); Hong Kong, pre-exposure (18.09, 8.19-39.96), exposed (9.32, 3.44-25.28), washout (7.69, 1.72-34.41). Following stratification for age and sex, the trends remained analogous to the main findings across all three populations. CONCLUSIONS: Although a positive association between initiating methylphenidate and the onset of myocardial infarction was observed, the risk was the highest in the period before its initiation. Thus, this multinational study suggests there was no causal relationship between methylphenidate and myocardial infarction among Asians.

Outcomes of acute cardiovascular events in rheumatoid arthritis and systemic lupus erythematosus: a population-based study.

OBJECTIVES: Patients with RA and SLE have an excess cardiovascular risk. We aimed to evaluate outcomes of acute cardiovascular events in these patients. METHODS: Using a nationwide database of Taiwan, we identified adult patients who experienced first-time acute myocardial infarction (n = 191 008), intracranial haemorrhage (n = 169 923) and ischaemic stroke (n = 486 890) over a 13-year period. Odds ratios (ORs) of in-hospital mortality and hazard ratios (HRs) of overall mortality and adverse outcomes during long-term follow-up in relation to RA and SLE were estimated with adjustment for potential confounders. RESULTS: In each cohort, 748, 410 and 1419 patients had established RA; 256, 292 and 622 patients had SLE. Among acute myocardial infarction patients, RA and SLE were associated with in-hospital mortality (RA: OR 1.61, 95% CI 1.33, 1.95; SLE: OR 2.31, 95% CI 1.62, 3.28) and overall mortality. Additionally, RA (HR 1.28, 95% CI 1.18, 1.38) and SLE (HR 1.46, 95% CI 1.27, 1.69) increased the risk of major adverse cardiac events. After intracranial haemorrhage, patients with RA and SLE had higher risks of in-hospital mortality (RA: OR 1.61, 95% CI 1.26, 2.06; SLE: OR 3.00, 95% CI 2.33, 3.86) and overall mortality. After ischaemic stroke, RA and SLE increased in-hospital mortality (RA: OR 1.45, 95% CI 1.15, 1.83; SLE: OR 2.18, 95% CI 1.57, 3.02), overall mortality and recurrent cerebrovascular events (RA: HR 1.10, 95% CI 1.002, 1.21; SLE: HR 1.31, 95% CI 1.14, 1.51), among which ischaemic stroke (HR 1.39, 95% CI 1.19, 1.62) was more likely to recur in SLE patients. CONCLUSION: Both RA and SLE are consistently associated with adverse outcomes following acute cardiovascular events, highlighting the necessity of integrated care for affected patients.

Two Decades of Research Using Taiwan's National Health Insurance Claims Data: Bibliometric and Text Mining Analysis on PubMed.

BACKGROUND: Studies using Taiwan's National Health Insurance (NHI) claims data have expanded rapidly both in quantity and quality during the first decade following the first study published in 2000. However, some of these studies were criticized for being merely data-dredging studies rather than hypothesis-driven. In addition, the use of claims data without the explicit authorization from individual patients has incurred litigation. OBJECTIVE: This study aimed to investigate whether the research output during the second decade after the release of the NHI claims database continues growing, to explore how the emergence of open access mega journals (OAMJs) and lawsuit against the use of this database affect the research topics and publication volume and to discuss the underlying reasons. METHODS: PubMed was used to locate publications based on NHI claims data between 1996 and 2017. Concept extraction using MetaMap was employed to mine research topics from article titles. Research trends were analyzed from various aspects, including publication amount, journals, research topics and types, and cooperation between authors. RESULTS: A total of 4473 articles were identified. A rapid growth in publications was witnessed from 2000 to 2015, followed by a plateau. Diabetes, stroke, and dementia were the top 3 most popular research topics whereas statin therapy, metformin, and Chinese herbal medicine were the most investigated interventions. Approximately one-third of the articles were published in open access journals. Studies with two or more medical conditions, but without any intervention, were the most common study type. Studies of this type tended to be contributed by prolific authors and published in OAMJs. CONCLUSIONS: The growth in publication volume during the second decade after the release of the NHI claims database was different from that during the first decade. OAMJs appeared to provide fertile soil for the rapid growth of research based on NHI claims data, in particular for those studies with two or medical conditions in the article title. A halt in the growth of publication volume was observed after the use of NHI claims data for research purposes had been restricted in response to legal controversy. More efforts are needed to improve the impact of knowledge gained from NHI claims data on medical decisions and policy making.

Intravenous Thrombolysis in Acute Ischemic Stroke After Idarucizumab Reversal of Dabigatran Effect: Analysis of the Cases From Taiwan.

BACKGROUND: Asians with atrial fibrillation carry a higher risk of ischemic stroke than non-Asians even under treatment of nonvitamin K antagonist oral anticoagulants. The purpose of the study was to observe the feasibility of intravenous thrombolytic therapy after administering a reversal agent, idarucizumab, in dabigatran-treated patients with acute ischemic stroke in Taiwan. METHODS: Dabigatran-treated patients with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (rt-PA) after idarucizumab reversal were enrolled in the retrospective nationwide study. The clinical data, treatment course, and outcomes were recorded. Stroke severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) score. Any intracerebral hemorrhage (ICH) after rt-PA was detected by neuroimaging studies. RESULTS: Ten dabigatran-treated patients (6 men, mean age 71.10 ± 7.96 years) with acute ischemic stroke were included. Before stroke, the mean CHA2DS2-VASc score was 4.50 ± 1.57 and 8 patients (80%) received dabigatran 110 mg twice daily. All patients were treated with 5 g idarucizumab, following which the activated partial thromboplastin time normalized. Intravenous rt-PA (mean dose .78 mg/kg) was initiated a mean time of 11.11 minutes after idarucizumab infusion. The NIHSS score improved significantly after thrombolysis (16.0 ± 6.67 at admission to 9.38 ± 4.75 at discharge, P = .016). ICH developed in 3 patients (30%). Two of them were asymptomatic and 1 patient suffered from symptomatic ICH leading to mortality. CONCLUSION: Our data reconfirmed the feasibility of intravenous rt-PA for Asian stroke patients after reversal of dabigatran effect with idarucizumab.

Medication Adherence and Stroke Prevention: What Real World Data Tells Us.

Medication adherence, by definition,(2) is "the extent to which a patient acts in accordance with the prescribed interval and dose of a dosing regimen." Poor medication adherence can interfere with the ability to treat many diseases, leading to greater complications and a lower quality of life.(3) In this issue of Acta Neurologica Taiwanica, Chen et al.(4) presented the inverse association between adherence of antithrombotic agents and poor outcomes after a first-ever ischemic stroke. The findings were consistent with Sung, et al.(5) that medication nonadherence are prevalent in young adults with a firstever stroke. The results by Chen, et al.(4) highlighted the importance of developing strategies to improve antithrombotic adherence. Besides, the risk-benefit profile of medication treatment must be considered and monitored for optimizing prescription in secondary stroke prevention. For those purposes, real-world data (RWD) derived from administrative claims database is becoming an efficient source of information.(6) The US Food and Drug Administration has also recognized the use of RWD to monitor post-marketing safety and adverse events and to make regulatory decisions of medicinal products.(7) Nonetheless, deriving RWD from administrative claims database should be held to an even higher scientific standard because of the greater potential for bias.(6) For example, the ascertainment of cases, coding for comorbidities, and handling of unmeasured confounders (e.g. disease severity) should follow those previously wellvalidated methods.(8-10) Besides, we should note that the adherence measured using claims data is the proportion of days covered with filled prescription. It might not be exactly equal to the real medication adherence behavior of the patients, as mentioned by Chen, et al.(4) Linking administrative claims database with other validated clinical databases (e.g. stroke registry) may improve the validity of a RWD study.(11) In the era of data science and artificial intelligence, we neurologists should endeavor to make the best use of all available electronic healthcare datasets, creating more useful RWD for our patients with strokes, as well as other neurological diseases.

Lower risk of dementia with pioglitazone, compared with other second-line treatments, in metformin-based dual therapy: a population-based longitudinal study.

AIMS/HYPOTHESIS: The effect of pioglitazone was compared with that of other second-line glucose-lowering drugs on the risk of dementia among individuals with type 2 diabetes receiving metformin-based dual therapy. METHODS: A total of 204,323 individuals with type 2 diabetes aged ≥18 years who were stable metformin users and dementia-free before the initiation of second-line glucose-lowering medication were identified in the period 2000-2011 from Taiwan's National Health Insurance Research Database and followed to the end of 2013. Primary analyses included 51,415 individuals aged ≥65 years without dementia events in the first year of second-line glucose-lowering treatment. Study subjects were classified into mutually exclusive groups according to various second-line glucose-lowering drugs to metformin. Cox proportional hazards models were applied to assess the time-to-event between propensity score-matched glucose-lowering treatment groups. RESULTS: Individuals aged ≥65 years on metformin + pioglitazone had a significantly lower risk of dementia compared with those on metformin + sulfonylurea (HR 0.56; 95% CI 0.34, 0.93), and a lower, but insignificant, risk of dementia compared with those on other metformin-based dual regimens (i.e. metformin + acarbose, metformin + meglitinide, metformin + insulin or metformin + dipeptidyl peptidase 4 inhibitors). Among individuals aged ≥18 years, there was also a decreased risk of dementia in those taking pioglitazone compared with those taking other second-line glucose-lowering drugs. A lower incidence of dementia was found in users of metformin + pioglitazone compared with users of metformin + rosiglitazone. CONCLUSIONS/INTERPRETATION: Pioglitazone as a second-line treatment after metformin might provide a protective effect on dementia risk among individuals with type 2 diabetes.

Effect of Rehabilitation Intensity on Mortality Risk After Stroke.

OBJECTIVE: To determine the relation between rehabilitation intensity and poststroke mortality. DESIGN: Retrospective cohort study. SETTING: Nationwide claims data. PARTICIPANTS: From Taiwan's National Health Insurance claims databases, patients (N=6737; mean age, 66.9y; 40.3% women) hospitalized between 2001 and 2013 for a first-ever stroke who had mild to moderate stroke and survived the first 90 days of stroke were enrolled. INTERVENTIONS: The intensity of rehabilitation therapy within 90 days after stroke was categorized into low, medium, or high based on the tertile distribution of the number of rehabilitation sessions. MAIN OUTCOME MEASURES: Long-term all-cause mortality. The Cox proportional hazard models with Bonferroni correction were used to assess the association between rehabilitation intensity and mortality, adjusting for age, comorbidities, stroke severity, and other covariates. RESULTS: Patients in the high-intensity group were younger but had a higher burden of comorbidities and greater stroke severity. During follow-up, the high-intensity group was associated with a significantly lower adjusted risk (hazard ratio [HR], .73; 95% confidence interval [CI], .63-.84) of mortality than the low-intensity group, whereas the medium-intensity group carried a similar risk of mortality (HR, 0.94; 95% CI, 0.84-1.06) compared with the low-intensity group. This association was not modified by stroke severity. CONCLUSIONS: Among patients with mild to moderate stroke severity, high-intensity rehabilitation therapy within the first 90 days was associated with a lower mortality risk than low-intensity therapy. Efforts to promote high-intensity rehabilitation therapy for this group of patients with stroke should be encouraged.

Subdural Hemorrhage in Patients with End-Stage Renal Disease Requiring Dialysis: A Single-Center Study.

PURPOSE: Patients with end-stage renal disease (ESRD) have higher risks of subdural hemorrhage (SDH) and subsequent 30-day mortality. However, evidences regarding optimal mode of dialysis therapy during acute management are sparse. We aimed to compare the outcomes of ESRD patients who received continuous peritoneal dialysis (CPD) or extended hemodialysis (EHD) after SDH and determined factors associated with 30-day mortality. METHODS: We retrospectively reviewed consecutive patients with SDH and ESRD in a medical center. The clinical parameters and outcomes were compared between CPD and EHD groups. Factors associated with 30-day mortality were analyzed. RESULTS: We reviewed 32 patients, including 22 received EHD, 8 received CPD, and 2 received continuous veno-venous hemodialysis. Neurosurgery was done in 9 (28%) of them. There was no significant difference in baseline parameters and outcomes between EHD and CPD groups. The overall 30-day mortality rate was 19%. Lower Glasgow coma scale (GCS, median [interquartile range]: 10 [7-12] vs. 15 [11-15], p = 0.02) and larger changes in absolute mean arterial pressure (MAP: 26.5 [10.5-46.0] vs. 7.5 [2.0-17.8] mmHg, p = 0.01) during the first dialysis therapy were noted in patients with 30-day mortality. In multivariate analysis, consciousness disturbance at presentation was an independent risk factor for 30-day mortality. CONCLUSION: Among ESRD patients with SDH, the 30-day mortality rates were similar between EHD and CPD groups. MAP change during dialysis might be an important modifiable risk factor for 30-day mortality, though the effect was not significant in multivariate analysis. Further prospective studies with larger sample size are warranted.

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.

Previously undiagnosed risk factors and medication nonadherence are prevalent in young adults with first-ever stroke.

PURPOSE: The incidence of stroke and prevalence of traditional vascular risk factors (VRFs) in young adults (age < 55 y) are both increasing. Young patients tend to be unaware of their VRFs and to have lower medication adherence. We examined how age affects the prevalence of previously undiagnosed VRFs and the extent of medication nonadherence among stroke patients. METHODS: Using Taiwan's National Health Insurance Research Database, we identified consecutive adult patients with first-ever stroke between 2000 and 2013. Diagnosis of hypertension, diabetes, and hyperlipidemia was ascertained using validated methods. We investigated (1) the proportion of patients who had undiagnosed VRFs within 3 years before stroke and (2) the proportion of nonadherence to medications among patients who had a previously diagnosed VRF. RESULTS: Among stroke patients with hypertension (n = 9722), diabetes (n = 4751), and hyperlipidemia (n = 4486), 24.9%, 20.8%, and 55.0%, respectively, had not been diagnosed before stroke, whereas 56.0%, 66.7%, and 32.5%, respectively, had been diagnosed at least 1 year before stroke. The proportions of medication nonadherence were 71.5%, 64.3%, and 88.4% in patients with previously diagnosed hypertension, diabetes, and hyperlipidemia, respectively. In multivariate analysis, younger age was independently associated with undiagnosed hypertension before stroke as well as medication nonadherence in patients with previously diagnosed hypertension or diabetes. CONCLUSIONS: Previously undiagnosed hypertension and nonadherence to treatment of hypertension and diabetes were more prevalent in young adult patients with first-ever stroke in Taiwan. Interventions targeting young people to promote early detection and adequate control of VRFs should be encouraged.

Risks of newly onset hemorrhagic stroke in patients with neovascular age-related macular degeneration.

PURPOSE: Age-related macular degeneration (AMD) is an eye disease causing blindness in the elderly. It shares many common possible pathogenic mechanisms with cardiovascular diseases. Many studies have discussed the association between AMD and stroke, but the results were inconsistent. Our aim was to determine the associations between neovascular AMD and the risk of stroke in the Taiwanese population. METHODS: This is a retrospective cohort study. We used claims data from National Health Insurance Research Database. Patients aged more than 45 years without stroke, myocardial infarction, or any AMD were selected from 2001 to 2008 and followed until 2010. The index date was defined as the date of nAMD diagnosis (ICD-9 code, 362.52). The comparison group was patients without an nAMD diagnosis with age- and sex-matched to nAMD subjects at a ratio of up to 10 to 1. Kaplan-Meier survival analysis and Cox regression analysis were used. The incidence of stroke events (ICD-9 codes, 430-434) and their subtypes (hemorrhagic and ischemic) were primary outcomes. Secondary outcomes included acute myocardial infarction (AMI), composite AMI/stroke, and all-cause mortality. RESULTS: Patients with nAMD had a higher risk of developing stroke, with an adjusted HR of 1.30 (95% CI, 1.01-1.68). A higher risk for hemorrhagic stroke (HR, 1.70, 95% CI, 1.03-2.83) was also found. No significant differences were observed in ischemic stroke, the composite of AMI/stroke, and all-cause mortality. CONCLUSIONS: Patients with nAMD had a significantly higher risk of developing stroke, which was driven mainly by the increased risk of developing the hemorrhagic subtype.

Validation of a novel claims-based stroke severity index in patients with intracerebral hemorrhage.

BACKGROUND: Stroke severity is an important outcome predictor for intracerebral hemorrhage (ICH) but is typically unavailable in administrative claims data. We validated a claims-based stroke severity index (SSI) in patients with ICH in Taiwan. METHODS: Consecutive ICH patients from hospital-based stroke registries were linked with a nationwide claims database. Stroke severity, assessed using the National Institutes of Health Stroke Scale (NIHSS), and functional outcomes, assessed using the modified Rankin Scale (mRS), were obtained from the registries. The SSI was calculated based on billing codes in each patient's claims. We assessed two types of criterion-related validity (concurrent validity and predictive validity) by correlating the SSI with the NIHSS and the mRS. Logistic regression models with or without stroke severity as a continuous covariate were fitted to predict mortality at 3, 6, and 12 months. RESULTS: The concurrent validity of the SSI was established by its significant correlation with the admission NIHSS (r = 0.731; 95% confidence interval [CI], 0.705-0.755), and the predictive validity was verified by its significant correlations with the 3-month (r = 0.696; 95% CI, 0.665-0.724), 6-month (r = 0.685; 95% CI, 0.653-0.715) and 1-year (r = 0.664; 95% CI, 0.622-0.702) mRS. Mortality models with NIHSS had the highest area under the receiver operating characteristic curve, followed by models with SSI and models without any marker of stroke severity. CONCLUSIONS: The SSI appears to be a valid proxy for the NIHSS and an effective adjustment for stroke severity in studies of ICH outcome with administrative claims data.