Adherence to Antipsychotic Drugs by Medication Possession Ratio for Schizophrenia and Similar Psychotic Disorders in the Republic of Korea: A Retrospective Cohort Study.

Objective: Pharmacotherapy is considered as an essential element in the treatment of psychotic disorders including schizophrenia. Discontinuation of antipsychotic drugs increases medical use and economic burden. Therefore, maintenance of medication is essential to reduce the social burden caused by schizophrenia and schizophrenia similar psychosis (SSP), and hence, it is important to investigate the rate at which pharmacotherapy is maintained. Therefore, this study aimed to examine the current status of drug compliance using national health insurance data. Methods: This was a retrospective cohort study, which analyzed data from the nationwide insurance claims database. A total of 343,134 patients who were newly diagnosed with schizophrenia and SSP during 2011-2015. The adherence to antipsychotic drugs was assessed by medication possession ratio (MPR) and the risk factors of poor adherence were defined as MPR < 40%. Results: The average of the MPRs was 45.8%, and the proportion of patients with less than 40% of MPR was 50.8%. It was found that female patients, the experience of "general hospital outpatient," "psychiatric hospital admission," general hospital admission," and patients receiving "health insurance" showed high risk of having statistically significant low MPR (< 40%). Conclusion: In this study, the drug adherence of schizophrenia and SSP patients currently under treatment, as estimated by MPR, was very low. However, it was also found that the MPR was high among patients receiving medical aid, with less medical expenses. Thus, it is possible to consider an institutional mechanism in which schizophrenia and SSP patients can be treated with less economic burden.

Endoscopic and Percutaneous Biliary Interventions after Liver Transplantation: Nationwide Data in Korea.

BACKGROUND/AIMS: Biliary complications including biliary strictures and bile leaks are the most common complications that occur after liver transplantation (LT). Endoscopic treatment with endoscopic retrograde cholangiography (ERC) is considered the first-line treatment, and percutaneous transhepatic cholangiography (PTC) can serve as an alternative or rescue therapy. However, nationwide clinical data on the frequency of ERC and PTC following LT have not yet been investigated. METHODS: Using the nationwide claims database, we investigated patients who underwent LT between 2012 and 2014 in Korea and followed them until 2015. We analyzed the prevalence and characteristics of patients and biliary procedures, including ERC and PTC implemented after LT. RESULTS: A total of 3,481 patients underwent LT during the 3-year study period. Among them, 3.0% of patients underwent biliary intervention postoperatively during the same hospitalization period, and 21.4% of patients received biliary intervention later on after initially being discharged from the hospital following LT. A total of 16.9% and 12.1% of patients underwent ERC and PTC after LT, respectively. The median period from LT to the first biliary intervention was 7.8 months (interquartile range, 3.5 to 14.6 months), and these patients underwent an average of 3.2±2.8 biliary procedures during the follow-up period. Patients undergoing living donor LT were more than twice as likely to undergo biliary procedures as those undergoing deceased donor LT (25.5% vs 12.1%). CONCLUSIONS: Approximately one-fourth of patients in Korea who underwent LT subsequently underwent ERC or PTC. Compared with deceased donor LT patients, those undergoing living donor LT underwent more biliary interventions and were more difficult to treat.

Endoscopic retrograde cholangiopancreatography-related adverse events in Korea: A nationwide assessment.

BACKGROUND: Although endoscopic retrograde cholangiopancreatography (ERCP) is a pivotal procedure for the diagnosis and treatment of a variety of pancreatobiliary diseases, it has been known that the risk of procedure-related adverse events (AEs) is significant. OBJECTIVE: We conducted this nationwide cohort study since there have been few reports on the real-world data regarding ERCP-related AEs. METHODS: Patients who underwent ERCP were identified between 2012 and 2015 using Health Insurance Review and Assessment database generated by the Korea government. Incidence, annual trends, demographics, characteristics according to the types of procedures, and the risk factors of AEs were assessed. RESULTS: A total of 114,757 patients with male gender of 54.2% and the mean age of 65.0 ± 15.2 years were included. The most common indication was choledocholithiasis (49.4%) and the second malignant biliary obstruction (22.8%). Biliary drainage (33.9%) was the most commonly performed procedure, followed by endoscopic sphincterotomy (27.4%), and stone removal (22.0%). The overall incidence of ERCP-related AEs was 4.7% consisting of post-ERCP pancreatitis (PEP; 4.6%), perforation (0.06%), and hemorrhage (0.02%), which gradually increased from 2012 to 2015. According to the type of procedures, ERCP-related AEs developed the most commonly after pancreatic stent insertion (11.4%), followed by diagnostic ERCP (5.9%) and endoscopic sphincterotomy (5.7%). Younger age and diagnostic ERCP turned out to be independent risk factors of PEP. CONCLUSIONS: ERCP-related AEs developed the most commonly after pancreatic stent insertion, diagnostic ERCP and endoscopic sphincterotomy. Special caution should be used for young patients receiving diagnostic ERCP due to increased risk of PEP.

Palliative endoscopic retrograde biliary drainage for malignant biliary obstruction in Korea: A nationwide assessment.

BACKGROUND: Malignant biliary obstruction (MBO) is usually caused by biliary tract cancer or pancreatic cancer. This study was performed to summarize the current situation regarding palliative endoscopic retrograde biliary drainage (ERBD) for MBO in Korea and to determine its clinical significance by analyzing representative nationwide data. METHODS: Patients that underwent palliative ERBD for MBO between 2012 and 2015 were identified using the Health Insurance Review and Assessment database, which covers the entire Korean population. We assessed clinical characteristics and complications and compared the clinical impacts of initial metal and plastic stenting in these patients. RESULTS: A total of 9,728 subjects (mean age, 65 ± 11.4 years; male, 61.4%) were identified and analyzed. The most common diagnosis was malignant neoplasm of liver and intrahepatic bile ducts (32.1%) and this was followed by extrahepatic or Ampulla of Vater cancer and pancreatic cancer. Initial plastic stent(s) placement was performed in 52.9% of the study subjects, and metal stent(s) placement was performed in 23.3%. The number of sessions of endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic biliary drainage (PTBD) was significantly higher in patients that underwent initial plastic stenting than in patients that underwent metal stenting (2.2 ± 1.7 vs 1.8 ± 1.4, P < 0.0001), but rates of post-ERCP pancreatitis, hospital days, and time to second ERCP or PTBD were not significantly different. CONCLUSION: This nationwide assessment study suggests that initial metal stenting is associated with fewer sessions of total ERCP or PTBD following the initial procedure, despite the preference for initial plastic stenting in Korea.

Three-year outcome of rapid HIV testing at public health centers in Seoul, Republic of Korea: a short report.

Before 2014, the only test used for anonymous voluntary human immunodeficiency virus (HIV) screening at public health centers (PHCs) in the Republic of Korea was an enzyme-linked immunosorbent assay (ELISA), which takes around 3 days to obtain results. In 2014, to encourage voluntary anonymous HIV screening tests, the Seoul Metropolitan Government adopted a rapid HIV screening test at PHCs. The rapid HIV screening test was introduced at four PHCs in 2014 and all 25 PHCs after 2015. We compared the numbers of HIV screening tests and confirmed positive individuals before and after introduction of the rapid HIV screening test. In 2012-2013, before the introduction of rapid HIV screening test, an average of 330 HIV screening tests were performed monthly (355 in 2012 and 305 in 2013) and 69 individuals were confirmed to have HIV in 2012 and 93 in 2013. After the introduction of the rapid HIV screening test, anonymous voluntary HIV screening increased to a monthly average of 447 tests in 2014, 2099 in 2015, and 2409 in 2016. These identified 38 new cases in 2014, 116 in 2015, and 143 in 2016. Adoption of the rapid HIV screening test has increased the number of HIV screening tests and confirmed cases.

Suboptimal medication adherence in young women living with HIV infection: a Korean nationwide claims study.

The epidemiological characteristics of women living with human immunodeficiency virus (HIV) infection have gained little attention as the numbers are small compared with men living with HIV in the Republic of Korea. However, these data are important to achieve effective HIV infection control and to consider the influence of socioeconomic status on HIV transmission. This study utilized the claims database of the Korean National Health Insurance system to analyze women with a newly diagnosed HIV infection during the period 2009-2016. Adherence to antiretroviral agents was calculated using the medication possession ratio. Among 677 women with a newly diagnosed HIV infection, 219 (32.4%) were over 50 years of age; 291 (43.0%) were identified as having acquired immune deficiency syndrome (AIDS). A total of 99 women (14.6%) were National Medical Aid beneficiaries. Optimal medical adherence >95% was found in 62.2% of subjects. Teenage years (odds ratio(OR) 14.9, 95% confidence interval (95CI) 4.9-44.8), AIDS (OR 1.7, 95CI 1.2-2.3), and low economic status requiring National Medical Aid (OR 3.0, 95CI 2.0-4.6) were associated to adherence. Diagnosis prior to 2012 was also associated with poor adherence. In women, particularly young patients with low economic status, extra attention is required to enhance adherence to prescribed medication.

Estimation of the Number of HIV Infections and Time to Diagnosis in the Korea.

BACKGROUND: Statistical data of undiagnosed people living with human immunodeficiency virus (PLHIV) are of great importance to human immunodeficiency virus (HIV) infection control. This study estimated the total number of PLHIV using nationwide claims data. METHODS: This study used data of the incident HIV cases identified by the National Health Insurance System between 2009 and 2015. The number of patients with acquired immune deficiency syndrome (AIDS) was identified by diagnoses or prescription records. The estimated number of PLHIV and the time to diagnosis were calculated from the incident numbers of HIV and AIDS cases using the HIV Modeling Tool of the European Center for Disease Prevention and Control. RESULTS: Between 2009 and 2015, a total of 7,033 PLHIV and 2,899 AIDS patients were diagnosed. In 2009, the number of incident HIV cases was 873 (460 AIDS patients), increasing to 995 (337 AIDS patients) in 2015. Besides, the estimated number of prevalent cases was 10,753 in 2009, compared to 14,880 in 2015. Patients visiting health facilities accounted for 42.9% (4,616/10,753) in 2009 and 64.1% (9,544/14,880) in 2015. In 2009, there were 8,363 (77.8%) undiagnosed HIV cases, experiencing a decline to 6,215 (41.8%) in 2015. It took a mean of 6.96 years to diagnose after HIV infection. CONCLUSION: This study estimates the total burden of HIV infection in Korea for the first time using an internationally recognized HIV modeling tool. Claims data can be used to estimate the number of undiagnosed cases by identifying the total number of PLHIV and AIDS patients visiting health facilities.

Annual Prevalence and Incidence of Schizophrenia and Similar Psychotic Disorders in the Republic of Korea: A National Health Insurance Data-Based Study.

OBJECTIVE: We conducted this study to address the incidence and prevalence of schizophrenia and similar psychosis in South Korea with Health Insurance Review and Assessment (HIRA) database. METHODS: We used HIRA database, which includes diagnostic information of nearly all Korean nationals to collect number of cases with diagnosis of schizophrenia and schizophrenia-similar disorders (SSP), including schizophreniform, acute/transient psychotic disorders, schizoaffective disorders, and other/unspecific nonorganic psychosis (ICD-10 codes F20/23/25/28/29) between 2010 and 2015. The annual prevalence and incidence were calculated using the population data from the Korean Statistical Office. RESULTS: The 12-month prevalence of SSP of Korea between 2010 and 2015 were 0.48-0.66%. The 12-month prevalence of schizophrenia were 0.40-0.52%; The annual incidence rates (IR) of SSP between 2010 and 2015 were 118.8-148.7 per 100,000 person-year (PY). For schizophrenia, IR per 100,000 PY were 77.6-88.5 between 2010 and 2015. CONCLUSION: The 12-month prevalence found in the present study was higher than that reported in community-based epidemiologic studies in South Korea but similar to those from other countries. The annual incidence of SSP and schizophrenia was found to steadily increase and was higher than that of other countries. The high incidence rate observed in the current study needs to be studied further.

Increasing burden of biliary tract infection caused by extended-spectrum beta-lactamase-producing organisms in Korea: A nationwide population-based study.

BACKGROUND AND AIM: Biliary tract infections (BTIs) are a major cause of bacteremia. The prevalence of antibiotic-resistant pathogens in BTI patients is reported to be increasing. We used a nationwide database to evaluate the prevalence of, and risk factors for, BTIs caused by extended-spectrum beta-lactamase-producing organisms (ESBL-PO) in Korea. METHODS: Patients with a BTI diagnosis, an admission history, a history of a BTI-related procedure, and antibiotic use for ≥ 4 days between 2007 and 2016 were identified from the Health Insurance Review and Assessment Service database. A BTI treated with carbapenems (BTI-TC) was used as the surrogate for a BTI caused by ESBL-PO. We conducted a multivariate logistic regression analysis to determine the risk factors for BTI-TC. RESULTS: In total, 341 002 patients were enrolled. The overall percentage of BTI-TC among BTIs was 2.4%, with an increasing annual trend (P < 0.0001). The risk of acute cholangitis caused by ESBL-PO increased significantly in men, older patients, patients with comorbidities, patients with a history of a biliary procedure within the previous year, and patients with a history of antibiotic use within the previous 90 days. Regarding antibiotic use, the patients at highest risk were those previously prescribed carbapenems (adjusted odds ratio, 4.77; P < 0.0001). CONCLUSIONS: The prevalence of BTIs caused by ESBL-PO has increased during the last 10 years. Initial carbapenem therapy should be considered for elderly patients with acute cholangitis if they have had a previous biliary procedure and/or a history of carbapenem administration within the previous 90 days.

Association of HIV-syphilis coinfection with optimal antiretroviral adherence: a nation-wide claims study.

Condomless sex is not totally discouraged after achieving undetectable human immunodeficiency virus (HIV) load, but the prevalence of sexually transmitted diseases (STDs) in the group is unknown. This study was retrospective in nature, using the claims database of the National Health Insurance system from 2008 to 2016. The clinical characteristics of people living with HIV with or without syphilis coinfection were analyzed. People with HIV and syphilis coinfection were divided into two groups according to antiretroviral therapy adherence, as optimal and suboptimal adherence groups by a medication possession ratio of 95%. Of the 9393 people living with HIV, 4536 (48.3%) were diagnosed with syphilis coinfection. Optimal adherence was associated with syphilis coinfection (odds ratio [OR] 1.18; 95% confidence interval [95CI] 1.08-1.30; p = .001). This suggests that unsafe sex occurs regardless of medication adherence. Being male, bacterial/protozoa STDs, and genital herpes virus infection were also risk factors for HIV-syphilis coinfection. Although HIV is unlikely to be transmittable when viral load is controlled, consistent use of condoms is necessary to prevent infection with syphilis.

Hypertension Risk with Abacavir Use among HIV-Infected Individuals: A Nationwide Cohort Study.

PURPOSE: A high risk of cardiovascular disease (CVD) is reported for HIV-infected individuals. While a link between abacavir and CVD risk is suggested, an association between abacavir and hypertension remains unclear. This study evaluated hypertension risk with abacavir use in comparison to non-abacavir antiretroviral treatment (ART). MATERIALS AND METHODS: From a nationwide cohort of HIV-infected individuals on their initial ART, 6493 who were free of hypertension at baseline were analyzed. The use of ART was treated as a time-varying covariate measured as a daily unit. Incidence rate of hypertension was calculated, and Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) with 95% confidence interval (CI) of incident hypertension overall and among subgroups. RESULTS: From the 6493 participants, 24072 person-years (PY) of follow-up were contributed during 2008-2016. The incidence rates of hypertension were 4.6 and 3.6 per 100 PY for abacavir and non-abacavir ART users, respectively. The population attributable fraction of abacavir use on hypertension was 12%. Abacavir exposure did not elevate the risk of hypertension among overall study population [HR, 1.2 (95% CI, 1.0-1.4), p=0.061]. However, those with poor ART adherence, defined as a medication possession ratio <50% [HR, 1.9 (95% CI, 1.5-2.4), p<0.0001] or requiring prophylactic antibiotics [HR, 1.2 (95% CI, 1.0-1.3), p=0.023], were at risk of hypertension induced by abacavir, as were men, individuals aged ≥40 years, and patients visiting tertiary hospitals in urban areas. CONCLUSION: When present, poor ART adherence, requiring prophylactic antibiotics, male sex, and older age may warrant additional concern for hypertension in patients treated with abacavir.

Adherence to antiretroviral therapy and factors affecting low medication adherence among incident HIV-infected individuals during 2009-2016: A nationwide study.

For ideal clinical benefit, human immunodeficiency virus (HIV)-infected individuals should receive continuous medication. This is the first nationwide antiretroviral therapy (ART) adherence study in Asia, where medication monitoring at national level is systemically available. We estimated the ART adherence of incident HIV-infected individuals and investigated factors affecting low medication adherence using the national health insurance (NHI) claims data from 2007 to 2016. Medication possession ratio (MPR) was used to measure medication adherence and risk factors were identified by multivariable logistic regression analysis. Of the 8,501 newly diagnosed HIV-infected individuals during 2009-2016 with at least one ART prescription, 70.4% of HIV patients had adequate adherence to ART defined as MPR ≥95%. Requiring prophylactic antibiotics, female gender, age of 0-19 and same or over 50 s compared to 30-39, and having a history of malignancy, lower socioeconomic status, not visiting tertiary hospital, and being diagnosed in the earlier years were risk factors for lower adherence (Odds ratio 1.7, 1.6, 1.6, 1.4, 1.6, 2.1, 1.2, and 1.6 to 3.8 respectively). Health authority should take into consideration of these modifiable and unmodifiable barriers to establish sustainable monitoring system at national level and to improve adherence.

Factors associated with intention to be tested for HIV among men who have sex with men in a country with a very low HIV prevalence.

This study examined factors associated with the intention to take an HIV test among men who have sex with men (MSM) in South Korea. An internet website-based survey was conducted among users of the only and largest online MSM website between 20 July 2016, and 20 August 2016. A total of 2915 participants completed the survey and answered questions related to sociodemographic information, health behaviors, sexual behaviors, and HIV testing history. Of these, 2587 (88.7%) participants responded as having an intention to take an HIV test. A multivariable logistic regression analysis revealed the following as having reduced the intention to undergo HIV testing: very good subjective health status and no sexual interactions during the last 6 months (Adjusted odds ratios [AOR] 0.45 and 0.54, respectively). In contrast, increased intention to take an HIV test was associated with being 20-29 years old, 30-39 years old, not paying or receiving money for sex, having a history of HIV testing, and taking an HIV test once per 12 months (AOR 2.64, 2.13, 1.54, 1.81, and 2.17, respectively). In conclusion, HIV testing among MSM in this study was associated with age, subjective health status, sex(es) of one's sexual partner(s) during the last 6 months, sexual risk behaviors, HIV testing history, and undergoing regular HIV testing.

Signal Detection of Imipenem Compared to Other Drugs from Korea Adverse Event Reporting System Database.

PURPOSE: To detect signals of adverse drug events after imipenem treatment using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD). MATERIALS AND METHODS: We performed data mining using KIDS-KD, which was constructed using spontaneously reported adverse event (AE) reports between December 1988 and June 2014. We detected signals calculated the proportional reporting ratio, reporting odds ratio, and information component of imipenem. We defined a signal as any AE that satisfied all three indices. The signals were compared with drug labels of nine countries. RESULTS: There were 807582 spontaneous AEs reports in the KIDS-KD. Among those, the number of antibiotics related AEs was 192510; 3382 reports were associated with imipenem. The most common imipenem-associated AE was the drug eruption; 353 times. We calculated the signal by comparing with all other antibiotics and drugs; 58 and 53 signals satisfied the three methods. We compared the drug labelling information of nine countries, including the USA, the UK, Japan, Italy, Switzerland, Germany, France, Canada, and South Korea, and discovered that the following signals were currently not included in drug labels: hypokalemia, cardiac arrest, cardiac failure, Parkinson's syndrome, myocardial infarction, and prostate enlargement. Hypokalemia was an additional signal compared with all other antibiotics, and the other signals were not different compared with all other antibiotics and all other drugs. CONCLUSION: We detected new signals that were not listed on the drug labels of nine countries. However, further pharmacoepidemiologic research is needed to evaluate the causality of these signals.

Signal Detection of Adverse Drug Reaction of Amoxicillin Using the Korea Adverse Event Reporting System Database.

We conducted pharmacovigilance data mining for a ß-lactam antibiotics, amoxicillin, and compare the adverse events (AEs) with the drug labels of 9 countries including Korea, USA, UK, Japan, Germany, Swiss, Italy, France, and Laos. We used the Korea Adverse Event Reporting System (KAERS) database, a nationwide database of AE reports, between December 1988 and June 2014. Frequentist and Bayesian methods were used to calculate disproportionality distribution of drug-AE pairs. The AE which was detected by all the three indices of proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) was defined as a signal. The KAERS database contained a total of 807,582 AE reports, among which 1,722 reports were attributed to amoxicillin. Among the 192,510 antibiotics-AE pairs, the number of amoxicillin-AE pairs was 2,913. Among 241 AEs, 52 adverse events were detected as amoxicillin signals. Comparing the drug labels of 9 countries, 12 adverse events including ineffective medicine, bronchitis, rhinitis, sinusitis, dry mouth, gastroesophageal reflux, hypercholesterolemia, gastric carcinoma, abnormal crying, induration, pulmonary carcinoma, and influenza-like symptoms were not listed on any of the labels of nine countries. In conclusion, we detected 12 new signals of amoxicillin which were not listed on the labels of 9 countries. Therefore, it should be followed by signal evaluation including causal association, clinical significance, and preventability.

Comparison of the prescribing pattern of bisphosphonate and raloxifene in Korean women with osteoporosis: from a national health insurance claims database.

This study aimed to evaluate the differences of prescribing pattern between bisphosphonate and raloxifene users among Korean women with osteoporosis, focusing on the underlying conditions, concurrent medications, nature of healthcare utilization, and regional disparity. We used the Health Insurance Review and Assessment Service National Patients Sample database of the year 2010. Study subjects were defined as female osteoporosis patients aged over 50 years with both the diagnosis of osteoporosis and prescriptions of bisphosphonate or raloxifene. The frequency and the proportion of bisphosphonate and raloxifene were compared using chi-square test and the trend of the proportion using the Cochran-Armitage test. Medications were quantified as defined daily doses per 1,000 patients per day. The prescription pattern was visualized by using the Quantum Geographic Information Systems program. Of the 1,367,367 people who utilized medical services in 2010, the final number of study subjects was 26,881--26,032 (96.8%) bisphosphonate and 849 (3.2%) raloxifene recipients. Raloxifene users were younger than bisphosphonate users and were more frequently patients with a lipid disorder (16.0% vs. 22.1%, p-value < 0.0001), rheumatic disease (4.0% vs. 6.1%, p-value = 0.0024), hot flash (1.8% vs. 6.1%, p <0.0001), and coronary artery disease (1.2% vs. 2.8%, p< 0.0001). The proportion of raloxifene users was higher in tertiary care institutions (21.6% vs. 44.7%, p-value < 0.0001). A regional distribution showed that raloxifene use was higher in the Seoul metropolitan area. These differences in demographic and clinical profiles of each recipient may influence prescription decisions.

Socioeconomic disparities in osteoporosis prevalence: different results in the overall Korean adult population and single-person households.

OBJECTIVES: The present study was conducted in order to examine the association between socioeconomic status (SES) and osteoporosis prevalence in Korea and to assess whether different associations are found in single-person households. METHODS: A cross-sectional population-based study was conducted using the Korea National Health and Nutrition Examination Survey, from 2008 to 2011. The study subjects were people aged ≥ 50 years with osteoporosis as defined by bone mineral density. Multivariate logistic models were used to estimate prevalence odds ratios (pORs) and 95% confidence intervals (CIs). Gender differences in the likelihood of osteoporosis were analyzed based on household income, education level, and residential area. RESULTS: There were 8221 osteoporosis patients aged ≥ 50 years, of whom 927 lived in single-person households. There was a gender-specific association between osteoporosis prevalence and all three SES factors that we analyzed: income, education, and residential area. After adjusting for age, SES, and health behaviors, including body mass index (BMI), low household income was only significantly associated with osteoporosis in men, whereas education level had an inverse relationship with osteoporosis only in women (p = 0.01, p < 0.001, respectively). However, after controlling for age and BMI, rural residency was only associated with osteoporosis in women living in single-person households (pOR, 1.59; 95% CI, 1.05 to 2.43). CONCLUSIONS: The Korean adult population showed a gender-specific relationship between SES and osteoporosis prevalence, with a different pattern found in single-person households.

Risk of gastrointestinal bleeding and cardiovascular events due to NSAIDs in the diabetic elderly population.

OBJECTIVE: We assessed gastrointestinal bleeding (GIB) and cardiovascular (CV) risks such as myocardial infarction or stroke associated with non-steroidal anti-inflammatory drug (NSAID) use among elderly patients with diabetes. METHODS: Using a nationwide claims database covering 2008-2012, we conducted a cohort study of patients with diabetes aged ≥65 years. Among the 117 610 patients, NSAID users and non-users were propensity score matched, excluding any who had experienced a potentially confounding event in the year prior to cohort entry. Multivariate Cox regression models treating death as competing risk were used. RESULTS: There were 2184 (1.86%) cases of GIB and NSAID users had an adjusted HR (aHR) of 1.68 (95% CI 1.54 to 1.83) of GIB risk after adjusting for age, sex, comorbidities and recent medications compared to NSAID non-users. There were 9333 (7.94%) cases of myocardial infarction or stroke with an aHR of 1.20 (95% CI 1.15 to 1.25). The risk of GIB was higher in patients with liver disease and renal failure, while that of CV events was higher in patients who received anticoagulants, antiplatelet agents, aspirin and selective serotonin reuptake inhibitors. The number needed to harm was 111 for GIB and 77 for CV events. Among different NSAIDs, nimesulide increased the risk of GIB and ketorolac increased the risk of CV events compared to celecoxib (aHR 2.60 and 3.13, respectively). CONCLUSIONS: Elderly patients with diabetes treating NSAIDs had a significantly higher risk of both upper GIB and CV events compared to NSAID non-users, and the risk varied among different NSAIDs regardless of cyclooxygenase-2 activity.

Effect of the calcineurin inhibitor FK506 on K+-Cl- cotransporter 2 expression in the mouse hippocampus after kainic acid-induced status epilepticus.

Calcineurin (CaN)-mediated excitotoxicity impairs γ-aminobutyric acid (GABA) transmission and induces neuronal apoptosis. Ca(2+)-dependent K(+)-Cl(-) cotransporter 2 (KCC2) participates in GABAergic inhibitory transmission. However, the mechanism by which CaN mediates GABA receptor-mediated KCC2 in seizures is not fully understood. In the present study, we investigated the altered expression of KCC2 and the effects of the CaN inhibitor FK506 on KCC2 expression in the mouse hippocampus following kainic acid (KA) treatment. FK506 was injected twice 24 h and 30 min before KA treatment and then mice were treated with KA and killed 2 days later. FK506 had anticonvulsant effect on KA-induced seizure activities. CaN cleavage was evident in the hippocampus 24 h after KA treatment. FK506 pretreatment blocked the truncation of CaN in the KA-treated hippocampus. Cresyl violet and TUNEL staining showed that FK506 prevented KA-induced hippocampal cell death. In particular, Western blot analysis showed that KCC2 expression was time dependent, with a peak at 6 h and a return to decreased levels at 48 h, whereas FK506 pretreatment inhibited the KA-induced decrease in KCC2 expression in the hippocampus. Immunofluorescence showed that FK506 pretreatment protected the loss of inhibitory GABAergic KCC2-expressing neurons following KA treatment. Taken together, these results provide evidence that altered KCC2 expression may be associated with Ca(2+)-mediated seizure activity and indicate that neuron-specific KCC2 may be involved in neuroprotection after seizures.

Angioplasty of middle cerebral artery stenosis improves recurrent hemichorea caused by basal ganglia hypoperfusion.

We report a case of intermittent hemichorea associated with severe stenosis in the proximal M1 portion of the middle cerebral artery. The movements disappeared after transluminal angioplasty and stenting with restoration of perfusion in the basal ganglia.