Trimetazidine Use and the Risk of Parkinsonism: A Nationwide Population-Based Study.

An association between trimetazidine (TMZ), an anti-anginal drug, and parkinsonism has been reported in a number of studies. However, evidence from studies with long-term follow-up and better validity is lacking. We investigated the risk of TMZ-associated parkinsonism, specifically the incidence rate, cumulative dose-response relationship, and combined effects with other parkinsonism-inducing medications. This propensity score-matched retrospective cohort study was conducted using 14-year health insurance claims data in South Korea. The risk of parkinsonism was evaluated using multivariate Cox proportional hazard regression analysis, adjusted for comorbidities and concurrent medications. A total of 9712 TMZ users and 29,116 matched non-TMZ users were included. TMZ users had a significantly higher incidence rate of parkinsonism than non-TMZ users (9.34 vs. 6.71 per 1000 person-years; p < 0.0001). TMZ use significantly increased the risk of parkinsonism (adjusted hazard ratio = 1.38; 95% confidence interval = 1.26-1.51). Increased risks were observed with accumulated doses of TMZ, as well as concurrent use of other parkinsonism-inducing medications. The findings indicate that TMZ use significantly increases the risk of parkinsonism in the South Korean population. Closer monitoring should be considered for TMZ users, especially for those who are older, using TMZ at high cumulative doses and other parkinsonism-inducing medications.

Calcium Channel Blocker-Associated Chyloperitoneum in Patients Receiving Peritoneal Dialysis: A Systematic Review.

Unlike chyloperitoneum associated with clinical conditions including cancer, cirrhosis, and traumatic surgery, calcium channel blocker (CCB)-associated chyloperitoneum is rarely discussed in comprehensive studies on chyloperitoneum. We aimed to investigate the prevalence and characteristics of CCB-associated chyloperitoneum in peritoneal dialysis (PD) patients. The MEDLINE, Embase, CENTRAL, CiNii, and RISS databases were systematically searched for clinical studies on CCB-associated chyloperitoneum in PD patients published up to 31 July 2018. A total of 17 studies (four cohort studies, one case series, and 12 case reports) were selected. Eight CCBs, namely amlodipine, benidipine, diltiazem, lercanidipine, manidipine, nifedipine, nisoldipine, and verapamil, were reported to be associated with chyloperitoneum; manidipine and lercanidipine were the most frequently reported. The average prevalence of chyloperitoneum for lercanidipine was 25.97% in three cohort studies, two of which had a moderate or high risk of bias. Most of the studies revealed chyloperitoneum development within 4 days of initiation of CCB therapy and chyloperitoneum disappearance within 24 h of CCB withdrawal. The results of this study emphasise on the need for awareness among healthcare professionals regarding CCB-associated chyloperitoneum in PD patients. Further studies elucidating the causality and clinical implication of CCB-associated chyloperitoneum are needed.

Association between Trimetazidine and Parkinsonism: A Population-Based Study.

BACKGROUND: The prevalence of drug-induced parkinsonism (DIP) has been reported with the use of trimetazidine (TMZ), an antianginal medication available in Asian and European countries. Very few studies have evaluated the association between DIP and TMZ use, and studies using population-based data from national databases are lacking. OBJECTIVES: To investigate the association between DIP and use of TMZ in patients with angina using data from a national healthcare claims database and to determine the predictive factors of DIP in TMZ use. METHODS: A cross-sectional study was conducted on patients aged 40 years or more diagnosed with angina, using the Korean National Healthcare claims 2014 database. The association between TMZ use and DIP was evaluated using multivariate logistic regression analysis, adjusting for confounders, including age; sex; insurance type; comorbidities; and concurrent medications known to be commonly associated with DIP, such as typical and atypical antipsychotics. RESULTS: Of the patients included in the study, 19% were prescribed TMZ. In addition, 2.5% of TMZ users had preexisting extrapyramidal and movement disorders. TMZ use was found to be a significant predictor of a new diagnosis of parkinsonism (adjusted OR [aOR] 1.39; 95% CI 1.06-1.81; p = 0.016). Age ≥65 years (aOR 2.07; 95% CI 1.13- 3.74; p = 0.017) and stroke as comorbid disease (aOR 3.23; 95% CI 1.87-5.61; p < 0.001) were also significantly associated with a new diagnosis of parkinsonism in TMZ users. CONCLUSIONS: Treatment with TMZ was a statistically significant predictor of a new diagnosis of parkinsonism. Efforts should focus on close monitoring of, and education on, TMZ use in relation to DIP in all patients who are prescribed TMZ, including those with preexisting extrapyramidal and movement disorders.

Nimesulide-induced hepatotoxicity: A systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the risk for hepatotoxicity with nimesulide, a non-steroidal anti-inflammatory drug (NSAID) available in Republic of Korea but withdrawn from the market in several countries. METHODS: A systematic review and meta-analysis were conducted of studies retrieved from PubMed, EMBASE, Cochrane, the Research Information Sharing Service and ClinicalTrials.gov up to September 2017. All studies reporting nimesulide-associated hepatotoxicity in patients as compared with the unexposed or the exposed to other NSAIDs were included. Studies using spontaneous reporting databases were included to estimate reporting odds ratio (ROR) of hepatotoxicity associated with nimesulide exposure. The association between nimesulide use and hepatotoxicity was estimated using relative risk (RR) and ROR with 95% confidence interval (CI). RESULTS: A total of 25 observational studies were eligible for review. In a meta-analysis of five observational studies, nimesulide was significantly associated with hepatotoxicity [RR 2.21, 95% CI 1.72-2.83]. From studies using spontaneous reporting databases (n = 6), rates of reported hepatotoxicity were significantly higher in patients using nimesulide, compared with those treated with other NSAIDs [pooled ROR 3.99, 95% CI 2.86-5.57]. Of a total of 33 patients from case studies and series, the majority (n = 28, 84.8%) were female, and the mean age (± standard deviation) was 56.8 (± 15.6) years. Almost half of the patients on nimesulide (45.5%) either required liver transplantation or died due to fulminant hepatic failure, of whom a third developed hepatotoxicity within less than 15 days of nimesulide administration. CONCLUSIONS: Our study findings support previous reports of an increased risk for hepatotoxicity with nimesulide use and add to existing literature by providing risk estimates for nimesulide-associated hepatotoxicity. As the limited number of studies with primarily observational study designs were included in the analysis, more studies are needed to further describe the effects of dose and length of treatment on the risk for hepatotoxicity.