Comparison of N-glycans expressed in tumor tissues with those expressed in adjacent non-tumor tissues of colorectal cancer patients
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BACKGROUND: The associations between colorectal cancer (CRC) progression and changes in N-glycan expression suggest the potential for new biomarkers and targeted cancer therapies. This study was performed to analyze N-glycans and to compare their expression profiles in tumor and corresponding adjacent non-tumor (control) tissues in stage I and IV CRC patients to examine N-glycans as potential prognostic markers. MATERIALS AND METHODS: Six adult CRC patients, including 3 in stage I and 3 in stage IV who underwent curative surgery were enrolled in this study. The tumor and control tissue samples were collected during surgery. Tissue samples were analyzed using liquid chromatography-tandem mass spectrometry as well as database searching. RESULTS: In this study, 76 N-glycans from 12 tissues of 6 CRC patients were profiled. There were 6 high mannose, 3 mannose, 1 core, 14 hybrid, 30 hybrid/complex, and 22 complex type N-glycans. There were 44 N-glycans in stage I control, 29 in stage I tumor, 43 in stage IV control, and 54 in stage IV tumor. Tumor- and stage-specific N-glycans were also identified. The relative abundance of N-glycans varied across the divided group. CONCLUSION: N-glycans presented only in stage I tumor from the biopsy sample for the diagnosis of CRC or in stage I control obtained during the surgery showed potential as biomarkers to predict CRC prognosis. Further high-throughput glycomic study should be performed with a larger sample size.
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Network analysis of drug-related problems in hospitalized patients with hematologic malignancies.

PURPOSE: Network analysis was conducted to systematically analyze the relationship between causative drugs and types of drug-related problems (DRPs) in hospitalized patients with hematologic malignancies. METHODS: A total of 1187 DRPs identified in hematology wards between 2013 and 2015 were analyzed. DRPs were classified into 11 sub-domains for problems and 35 sub-domains for causes according to Pharmaceutical Care Network Europe classification. Causative drugs were classified by Anatomical Therapeutic Chemical code. Network analytic tool was used to represent the relationship between drugs, causes, and problems. In-degree centrality (CD-in) was calculated to identify major causes of DRPs. RESULTS: The following drugs accounted for more than 5% of DRP, including antibacterials (J01, 26.5%), drugs for acid-related disorders (A02, 11.5%), antiemetics (A04, 9.7%), antifungals (J02, 8.8%), and antineoplastic agents (L01, 7.0%). Inappropriate combinations (C1.3, CD-in of 161) of drugs for acid-related disorders, antifungals, and antineoplastic agents were major causes of DRPs and induced non-optimal effects of drug treatment (P1.2). Inappropriate dose adjustments (C3.6, CD-in of 151) of antibacterials lowered effects (P1.2) and increased side effects (P2.1). Missing necessary synergistic or preventive drugs, especially antiemetics, (C1.8, CD-in of 54) resulted in untreated indication (P1.4). CONCLUSIONS: DRPs were mainly related to medications for supportive care. More attention should be paid to interactions of drugs used for acid-related disorders, dose adjustment of antibacterials, and omission of antiemetics in hospitalized patients with hematologic malignancy.

Global perspectives on ensuring the safety of pharmaceutical products in the distribution process
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OBJECTIVE: The distribution of counterfeit or falsified drugs is increasing worldwide. This can contribute to the high burden of disease and cost to society and is of global concern with the worldwide circulation of pharmaceuticals. The preparation and implementation of good distribution practice should be one of the most important aspects of ensuring safe drug circulation and administration. This research aimed to compare and analyze good distribution practice guidelines from advanced countries and international organizations, and to evaluate the status of the current good distribution practice guidelines in the world. MATERIALS AND METHODS: Advanced pharmaceutical countries and international organizations, such as the World Health Organization, European Union, Pharmaceutical Inspection Co-operation Scheme, United States of America, Canada, and Australia, which have stable good distribution practice guidelines and public confidence, were included in the analysis. RESULTS: The World Health Organization and European Union guidelines are models for standardized good distribution practice for nations worldwide. The United States of America has a combination of four different series of distribution practices which have a unique structure and detailed content compared to those of other countries. The Canadian guidelines focus on temperature control during storage and transportation. The Australian guidelines apply to both classes of medicinal products and medical devices and need separate standardization. CONCLUSION: Transparent information about the Internet chain, international cooperation regarding counterfeiting, a high-standard qualification of sellers and customers, and technology to track and trace the whole life cycle of drugs should be the main focus of future good distribution practice guidelines worldwide.
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Geographic variations in antibiotic prescription for pediatric acute upper respiratory tract infections in South Korea.

OBJECTIVE: This study aimed to investigate the factors affecting the geographic differences in antibiotic prescription rates in pediatric upper respiratory tract infections (URI) patients in South Korea. MATERIALS AND METHODS: We performed a nationwide cross-sectional study using 228 administrative districts of Korea, which are the unit of analysis. Prescription rate of antibiotics, the outcome variable, was measured as the proportion of antibiotic prescription days out of total visit days for the treatment of acute URIs using National Health Insurance Service (NHIS) claims data for 2012. Multivariate regression analysis was performed to identify factors affecting geographic variation in antibiotic prescription rates. RESULTS: The socioeconomic status of the district, as measured by the amount of local property tax payable and the proportion of individuals with higher level of education, were negatively correlated with prescription rate. The degree of competition in the hospital market within a district was positively associated with it. Patients living in areas with better access to family medicine physicians and those living in rural areas were less likely to use antibiotics to treat URIs. CONCLUSION: Our findings indicate the importance of considering demand factors as well as supply factors when developing intervention strategies for antibiotic overuse.
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Independent operation of implicit working memory under cognitive load.

Implicit working memory (WM) has been known to operate non-consciously and unintentionally. The current study investigated whether implicit WM is a discrete mechanism from explicit WM in terms of cognitive resource. To induce cognitive resource competition, we used a conjunction search task (Experiment 1) and imposed spatial WM load (Experiment 2a and 2b). Each trial was composed of a set of five consecutive search displays. The location of the first four displays appeared as per pre-determined patterns, but the fifth display could follow the same pattern or not. If implicit WM can extract the moving pattern of stimuli, response times for the fifth target would be faster when it followed the pattern compared to when it did not. Our results showed implicit WM can operate when participants are searching for the conjunction target and even while maintaining spatial WM information. These results suggest that implicit WM is independent from explicit spatial WM.

Meta-analysis of the Efficacy and Safety of Secukinumab for the Treatment of Plaque Psoriasis.

BACKGROUND: In January 2015, US FDA approved secukinumab, a human interleukin-17A (IL-17A) antagonist, for the treatment of plaque psoriasis. OBJECTIVE: To provide unbiased drug information about the efficacy and safety of secukinumab for the treatment of moderate to severe plaque psoriasis by performing meta-analysis. METHODS: PubMed and EMBASE database searches were conducted. Among the literatures retrieved, relevant Phase III clinical trials were analyzed. Statistical analysis of the data was performed by RevMan. RESULTS: Four pivotal and three non-pivotal Phase III clinical trials were retrieved. All the trials evaluated the efficacy and safety of secukinumab for the treatment of moderate to severe plaque psoriasis with two co-primary endpoints: proportions of Psoriasis Area and Severity Index (PASI) responders and Investigator's Global Assessment (IGA) responders. The overall odd ratios for proportions of PASI responders and IGA responders in secukinumab-containing arm were 65.6 and 62.5 compared to the placebo arm, respectively. Secukinumab was superior to etanercept resulting in both of the odd ratios being 3.7 compared to the etanercept. Secukinumab was generally well tolerated during the one year trial. However, as with other monoclonal antibody medications, vulnerability of respiratory infection (especially nasopharyngitis) was reported as most common adverse event. CONCLUSIONS: Meta-analysis of the seven Phase III clinical trials resulted in superiority of secukinumab over etanercept in terms of the efficacy and safety. However, long-term safety data is lacking at this time so post-marketing surveillance should be performed for any adverse events associated with the use of this new biological medication.

Construction of a database for published phase II/III drug intervention clinical trials for the period 2009-2014 comprising 2,326 records, 90 disease categories, and 939 drug entities.

OBJECTIVES: To construct a database of published clinical drug trials suitable for use 1) as a research tool in accessing clinical trial information and 2) in evidence-based decision-making by regulatory professionals, clinical research investigators, and medical practitioners. MATERIALS: Comprehensive information obtained from a search of design elements and results of clinical trials in peer reviewed journals using PubMed (http://www.ncbi.nlm.ih.gov/pubmed). METHOD: The methodology to develop a structured database was devised by a panel composed of experts in medical, pharmaceutical, information technology, and members of Ministry of Food and Drug Safety (MFDS) using a step by step approach. A double-sided system consisting of user mode and manager mode served as the framework for the database; elements of interest from each trial were entered via secure manager mode enabling the input information to be accessed in a user-friendly manner (user mode). Information regarding methodology used and results of drug treatment were extracted as detail elements of each data set and then inputted into the web-based database system. RESULTS: Comprehensive information comprising 2,326 clinical trial records, 90 disease states, and 939 drugs entities and concerning study objectives, background, methods used, results, and conclusion could be extracted from published information on phase II/III drug intervention clinical trials appearing in SCI journals within the last 10 years. The extracted data was successfully assembled into a clinical drug trial database with easy access suitable for use as a research tool. The clinically most important therapeutic categories, i.e., cancer, cardiovascular, respiratory, neurological, metabolic, urogenital, gastrointestinal, psychological, and infectious diseases were covered by the database. Names of test and control drugs, details on primary and secondary outcomes and indexed keywords could also be retrieved and built into the database. The construction used in the database enables the user to sort and download targeted information as a Microsoft Excel spreadsheet. CONCLUSION: Because of the comprehensive and standardized nature of the clinical drug trial database and its ease of access it should serve as valuable information repository and research tool for accessing clinical trial information and making evidence-based decisions by regulatory professionals, clinical research investigators, and medical practitioners.

Vitamin D Receptor-Mediated Upregulation of CYP3A4 and MDR1 by Quercetin in Caco-2 cells.

To examine whether quercetin interacts with vitamin D receptor, we investigated the effects of quercetin on vitamin D receptor activity in human intestinal Caco-2 cells. The effects of quercetin on the expression of the vitamin D receptor target genes, vitamin D3 24-hydroxylase, cytochrome P450 3A4, multidrug resistance protein 1, and transient receptor potential vanilloid type 6 were measured using quantitative polymerase chain reaction. The vitamin D receptor siRNA was used to assess the involvement of the vitamin D receptor. Vitamin D receptor activation using a vitamin D responsive element-mediated cytochrome P450 3A4 reporter gene assay was investigated in Caco-2 cells transfected with human vitamin D receptor. We also studied the magnitude of the vitamin D receptor activation and/or synergism between 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] and quercetin-like flavonoids. Slight but significant increases in the mRNA expression of cytochrome P450 3A4, vitamin D3 24-hydroxylase, multidrug resistance protein 1, and transient receptor potential vanilloid type 6 were observed after 3 days of continual quercetin treatment. The silencing effect of vitamin D receptor by vitamin D receptor siRNA in Caco-2 cells significantly attenuated the induction of the vitamin D receptor target genes. Moreover, quercetin significantly enhanced cytochrome P450 3A4 reporter activity in Caco-2 cells in a dose-dependent manner, and the expression of exogenous vitamin D receptor further stimulated the vitamin D receptor activity. Quercetin-like flavonoids such as kaempferol stimulated the vitamin D receptor activity in a manner similar to that seen with quercetin. Taken together, the data indicates that quercetin upregulates cytochrome P450 3A4 and multidrug resistance protein 1 expression in Caco-2 cells likely via a vitamin D receptor-dependent pathway.

Prediction of the tacrolimus population pharmacokinetic parameters according to CYP3A5 genotype and clinical factors using NONMEM in adult kidney transplant recipients.

PURPOSE: Tacrolimus is a commonly used immunosuppressant in solid organ transplantation recipients, but it is characterized by a narrow therapeutic range and large inter-individual variability. The purpose of this study was to establish a population pharmacokinetic (PK) model of tacrolimus and evaluate the influence of clinical covariates, including the genetic polymorphisms of the cytochrome P450 3A5 gene (CYP3A5) and gene encoding P-glycoprotein (ABCB1), on the PK parameters in adult Korean kidney transplant recipients. METHODS: Clinical data were collected retrospectively for 400 days after the initiation of a tacrolimus-based immunosuppression therapy. Data from 2,788 trough blood samples obtained from 80 subjects were used to perform a population PK analysis with a nonlinear mixed-effect model (NONMEM). RESULTS: The estimated population mean values of clearance (CL/F) and volume of distribution (V/F) were 22.9 L/h and 716 L, respectively, and the k(a) was fixed to 4.5 h⁻¹. The CYP3A5 genotype, hematocrit level, and post-operative days were identified as the main covariates that influence CL/F, and body weight was found to have a significant effect on V/F. Other covariates, including ABCB1 genotype, corticosteroid dosage, sex, and other clinical data, did not contribute to the pharmacokinetics of tacrolimus. CONCLUSIONS: This tacrolimus population PK model will be a valuable tool in developing rational guidelines and provides a basis for individualized therapy after kidney transplantation in clinical settings of Korea.

Clinical and genetic factors affecting tacrolimus trough levels and drug-related outcomes in Korean kidney transplant recipients.

PURPOSE: The purpose of this study was to characterize the effects of clinical and genetic variables on the pharmacokinetics and complications of tacrolimus during the first year after kidney transplantation. METHODS: One hundred and thirty-two Korean kidney recipients who received tacrolimus were genotyped for ABCB1 (exons 12, 21, and 26) and CYP3A5 (intron 3). Tacrolimus trough levels, dose, or dose-adjusted trough levels and complications were compared among patients during the early stage (3, 7, 14, 30, and 90 days) and up to 1 year according to the genotypes. RESULTS: A donor source-adjusted linear mixed model with multilevel analysis adjusting for age, body weight, hematocrit, and serum creatinine showed that CYP3A5 genotype is associated with dose-adjusted level of tacrolimus (p < 0.001). The influence of ABCB1 polymorphisms on the pharmacokinetics or complications of tacrolimus was less certain in our study. The incidence of acute rejections was significantly higher in recipients of cadaveric donor kidney (p < 0.05). CONCLUSIONS: A generalized estimating equation model analysis showed that alopecia and hyperlipidemia were associated with dose-adjusted level of tacrolimus (p < 0.001). Genotype of CYP3A5 variants along with significant clinical covariates may be useful in individualizing tacrolimus therapy in kidney transplantation patients.

Emotion Perception Rules Abide by Cultural Display Rules.

The current study compared emotion perception in two cultures where display rules for emotion expression deviate. In Experiment 1, participants from America and Korea played a repeated prisoner's dilemma game with a counterpart, who was, in actuality, a programmed defector. Emotion expressions were exchanged via emoticons at the end of every round. After winning more points by defecting, the counterpart sent either a matching emoticon (a joyful face) or a mismatching emoticon (a regretful face). The results showed that Americans in the matching condition were more likely to defect, or to punish, compared to those in the mismatching condition, suggesting that more weight was given to their counterpart's joyful expression. This difference was smaller for Koreans, suggesting a higher disregard for the outward expression. In a second, supplementary experiment, we found that Korean participants were more likely to cooperate in the mismatching or regretful condition, when they thought their counterpart was a Westerner. Overall, our data suggest that emotion perception rules abide by the display rules of one's culture but are also influenced by the counterpart's culture.

The effectiveness of interprofessional education programs for medical, nursing, and pharmacy students.

PURPOSE: This study is to develop an interprofessional education (IPE) program for medical, nursing, and pharmacy students and to analyze the effectiveness. METHODS: Subjects consisted of 116 students (41 medical, 46 nursing, and 29 pharmacy students) enrolled in their final year. Subjects were randomly assigned to either the intervention group or the control group, with 58 in each group. A pretest-posttest control group design was used. The program was operated for a single day, and consisted of small-group activities and role-play. We utilized the following tools: Perceptions towards Interprofessional Education (PIPE), Self-Efficacy for Interprofessional Experiential Learning (SEIEL), and Perception towards Interprofessional Competency (PIC). We used t-test and analysis of covariance for analysis. RESULTS: The PIPE tool revealed that the scores of the intervention group were significantly higher than those of the control group (p=0.000). The result was the same when the scores were categorized into the groups medical students (p=0.001), nursing students (p=0.000), and pharmacy students (p=0.005). The SEIEL study also indicated the intervention group scored significantly higher than the control group (p=0.000). However, pharmacy students did not reveal significant (p=0.983). The intervention group scored significantly higher than the control group in the PIC. A concluding survey of the intervention group indicated that most students were satisfied with the IPE program. CONCLUSION: We hope this study will provide useful information for designing and improving IPE programs in other universities.

Perception of interprofessional education and educational needs of students in South Korea: A comparative study.

Due to the recent emphasis on the importance of interprofessional education (IPE) in healthcare fields, interest in IPE introduction is increasing in South Korea. The purpose of this study was to examine the differences in perceptions of medical, nursing, and pharmacy students regarding IPE. Also, the study aimed at identifying the priority rankings of educational needs by analyzing the differences between students' perceptions of the importance level and the present level for each interprofessional competency. A cross-sectional study was carried out using a survey. A total of 1,500 questionnaires were distributed, of which 1,084 were returned (response rate, 72.3%). The participants were 559 medical, 393 nursing, and 96 pharmacy students. The questionnaire comprised items on the students' perception of IPE and their interprofessional competency. The questionnaire comprised 12 items on their IPE perception and 9 items on their interprofessional competency. These items were developed by examining the content validity by medical educational specialists and conducting a factor analysis for verification. Data were analyzed using the t-test and ANOVA, and Borich's formula was used to calculate the rank of educational needs.89.6% did not know the meaning of IPE. The difference in students' perception of IPE was not significant by grade. Further, the level of IPE perception was higher for female than male students and for students who knew the meaning of IPE than those who did not. The nursing students' perception of the importance, preference, and effectiveness of IPE was the highest, whereas medical students' perception was the lowest. All students perceived their present level to be lower than the importance level for each interprofessional competency. Interprofessional communication skills (6.791) were highly necessary for students. These results will serve as baseline information for developing IPE programs in South Korea.

Perceptions of the interprofessional education of the faculty and the level of interprofessional education competence of the students perceived by the faculty: a comparative study of medicine, nursing, and pharmacy.

PURPOSE: This study will compare differences in perception of interprofessional education (IPE) in the faculty of medicine, nursing, and pharmacy. It will also analyze differences in the level of importance of IPE competences and the present competence levels of their students perceived by the faculty. METHODS: The study included 115 participants from the faculty of medicine, 31 from nursing, and 23 from pharmacy. The surveys contained 21 questions on their perceptions of IPE, and perception on the nine competences of IPE. The results were analyzed using analysis of variance and χ2 analysis, and the Borich coefficient was calculated to identify the educational order of priority from the competence levels of their student of IPE. RESULTS: Participants of 14.8% responded that they were aware of IPE, 95.8% responded that they did not have experience in IPE, and 95.8% responded that IPE was necessary. Among the subfactors of perception of IPE, the faculty of medicine had significantly lower perceptions of the importance, effectiveness, and support of IPE (p<0.001). The present competence levels of their students were significantly lower (p<0.001) than the level of importance of IPE competences perceived by the faculty, and its perception was at its lowest in the faculty of medicine. The needs assessment of the IPE program was in the order of communication skills (10.210), conflict-solving skills (10.114), problem-solving skills (9.319), empathy skills (9.110), and collaborative leadership (8.624) among the nine competences. CONCLUSION: This study will contribute to providing basic data needed to develop faculty development programs on IPE and IPE programs for their students.

Simple action planning can affect attentional allocation in subsequent visual search.

Previous research has shown that mental representations of actions can influence performance on relevant tasks or dimensions even when there is no overt execution of the action. In this study, we examined whether cognitive processes prior to the physical execution of an action can elicit attentional bias towards irrelevant tasks or dimensions of that action. Participants performed two independent tasks-an action task and a search task-where they were instructed to plan an action and execute the action following the visual search task. We found that the same features of the object were prioritized in the subsequent search task when participants had planned an action response on the object in comparison to when they had not. This effect occurred even when the feature was irrelevant to the tasks or required action. Furthermore, the effect of action planning without physical response was found to be comparable to the effect of physical response. These results suggest that planning of a simple action can induce attentional bias to irrelevant features of objects even without physical action.

Anti-Inflammatory Effect of Sulforaphane on LPS-Activated Microglia Potentially through JNK/AP-1/NF-κB Inhibition and Nrf2/HO-1 Activation.

Sulforaphane (SFN), a potent nuclear factor erythroid 2-related factor 2 (Nrf2) activator, is present in the species of the Brassicaceae, especially in broccoli sprouts. In this study, the effects of SFN against microglial activation and inflammation, and the potential mechanisms involved, were analyzed. As mitogen-activated protein kinase (MAPK) signaling plays a key role in microglial activation and inflammation, we focused on the role of SFN in regulating the MAPK signaling regulation of the inflammatory and anti-inflammatory cascades in lipopolysaccharide (LPS)-activated microglia. The anti-inflammatory and immunomodulatory effects of SFN were explored by evaluating the expression and secretion of inflammatory proteins, cytokines, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and activator protein-1 (AP-1) under pre- and post-treatment conditions. Under the SFN pre- and post-treatment conditions, the MAPK phosphorylation levels were significantly reduced in both acutely and chronically activated microglial cells. SFN also reduced the c-Jun N-terminal kinase (JNK) phosphorylation levels, which subsequently reduced NF-κB and AP-1 signaling. As a result, the expression of the inflammatory mediators (iNOS, COX-2, NO, and PGE2) and proinflammatory cytokines (TNF-α, IL-6, and IL-1ß) was decreased. At the same time, SFN increased the expression of Nrf2 and heme oxygenase-1 (HO-1) as well as the production of the anti-inflammatory cytokines IL-10 and IL-4. In conclusion, this study demonstrated that SFN exerts an anti-neuroinflammatory effect on microglia through JNK/AP-1/NF-κB pathway inhibition and Nrf2/HO-1 pathway activation.

Effect of glutathione S-transferase genetic polymorphisms on busulfan pharmacokinetics and veno-occlusive disease in hematopoietic stem cell transplantation: A meta-analysis.

This meta-analysis was conducted to derive an integrated conclusion about the influence of glutathione S-transferase (GST) genetic polymorphisms on busulfan pharmacokinetic (PK) parameters and veno-occlusive disease (VOD). Studies which analysed the effect of GST genetic polymorphisms on area under the curve (AUC), clearance (CL) or VOD were searched for and selected. A pooled analysis was conducted using Comprehensive Meta-Analysis programme. Nineteen studies were included in this meta-analysis. GSTA1*B and GSTM1 null genotypes significantly decreased CLIV of busulfan (standardized difference in means (SDM) = -1.103; P = 0.019 and SDM = -0.418; P = 0.002, respectively). GSTA1*B significantly increased AUCIV of busulfan (SDM = 0.832; P = 0.046), whereas GSTM1 did not (SDM = 0.155; P = 0.478). The PK parameters of oral busulfan did not differ according to GST genotype. GSTA1, GSTM1 and GSTP1 were not significantly associated with VOD occurrence. GSTA1 and GSTM1 genotypes affected CLIV of busulfan, but only GSTA1 affected AUCIV . There was no significant difference in the PK parameters of oral busulfan (CLPO and AUCPO ) and VOD when only GST genotypes were considered.

Perspectives of Non-Pharmacy Professionals in Long-Term Care Facilities on Pharmacist-Involved Medication Management in South Korea: A Qualitative Study.

Despite a rapid increase in both the number of long-term care facilities (LTCFs) and their residents in recent years, the concept of pharmacist-involved medication management is relatively new in South Korea. The objective of this study was to identify the perspectives of non-pharmacy professionals regarding the development of pharmacist-involved medication management in LTCFs. Employing a snowball sampling strategy, this study relied on semi-structured, one-on-one, in-depth interviews with twelve non-pharmacy professionals in LTCFs. The inductive thematic analysis and the constant comparative method were employed for the analysis. Participants revealed the need for pharmacist-involved medication management systems in LTCFs at the intrinsic and environmental levels. Through pharmacist-involved medication management, participants desired "medication review/reconciliation" and "pharmaceutical education/counseling". The barriers to be overcome included "the authorization of pharmacists' roles", "the financial stability of LTCFs", "role awareness among coworkers", and "the professional development of pharmacists". In this study, we advanced our understanding of non-pharmacy professionals' perceptions of pharmacist-involved medication management in LTCFs. The results of this study can be applied in other Asian countries where the development of pharmacist-involved medication management for the institutionalized elderly is relatively new.

Differences in preventing new-onset cardiovascular events with statin therapy in seniors aged 75 years and over: A cohort study in the South Korean National Health Insurance Database.

The aim of this cohort study was to compare the effectiveness of statin regimens for primary prevention among seniors aged ≥ 75 years. Seniors aged 75-100 years for whom statin therapies for primary prevention were newly initiated between 1 January 2009 and 31 December 2011, and who continued the same statin regimen during the first year after the index date were identified using the claims data from the South Korean National Health Insurance Database. A propensity score matching and multivariable Cox proportional hazards model were developed to evaluate adjusted ischaemic cardiovascular-cerebrovascular event (CCE) risk and all-cause mortality risk for all patients, as well as for subgroups. A total of 5629 older patients aged 75-100 years were included in the study population. Compared to moderate-intensity statin therapy, low-intensity statin therapy was significantly associated with increased risk of ischaemic CCEs, while high-intensity statin therapy was associated with reduced risk of ischaemic CCEs; however, compared to moderate-intensity statin therapy, both low-intensity and high-intensity statin therapies were associated with increased risk of all-cause mortality. For the 4689 older patients who regularly received moderate-intensity statin therapy including 10 mg atorvastatin, 20 mg atorvastatin, 10 mg rosuvastatin or 20 mg simvastatin for primary prevention, multivariable regression adjusting for potential covariates revealed no significant difference in ischaemic CCEs or all-cause mortality between the moderate-intensity statin users and 10 mg atorvastatin users both before and after propensity scoring matching. No significant heterogeneity was detected in the patient subgroups. The results of this study based on real-world data can supply evidence-based reasons for choice of statin regimen for the primary prevention of CCEs in older people aged ≥ 75 years.

The effect of selective serotonin reuptake inhibitors on major adverse cardiovascular events: a meta-analysis of randomized-controlled studies in depression.

It has been reported that selective serotonin reuptake inhibitors (SSRIs) might induce major adverse cardiovascular events (MACE), but the association between the use of SSRIs and MACE has not been elucidated as yet. Therefore, the aim of this study was to evaluate the association between the use of SSRIs and MACE in depressed patients with previous cardiovascular events. Two researchers independently selected randomized-controlled studies (RCTs) according to the predefined inclusion criteria and evaluated the quality of articles. A quantitative analysis was carried out to estimate pooled risk ratios (RRs) for the association between the use of SSRIs and MACE. Ten RCTs were selected in the final analysis. The use of SSRIs in depressed patients with previous cardiovascular events significantly decreased the risk of MACE [RR: 0.74; 95% confidence interval (CI): 0.55-0.99]. The risk of myocardial infarction was also reduced significantly (RR: 0.59, 95% CI: 0.37-0.93), associations with stroke and all-cause-death (cardiac or other causes): risk of stroke (RR: 0.88, 95% CI: 0.35-2.25) or all-cause death (RR: 0.83; 95% CI: 0.66-1.05). This meta-analysis suggests that the use of SSRIs decreased the risk of MACE by significantly reducing the risk of myocardial infraction in patients with depression and previous cardiovascular events.