Kim JA, et al. J Korean Med Sci. 2017 May;32(5):718-728. https://doi.org/10.3346/jkms.2017.32.5.718

Background: Benzodiazepines are frequently prescribed during pregnancy; however, evidence about possible teratogenicity is equivocal. We aimed to evaluate the association between first-trimester benzodiazepine use and the risk of major congenital malformations.Methods and findings: Using Korea’s nationwide healthcare database, we conducted a population-based cohort study of women who gave birth during 2011 to 2018 and their live-born infants. The exposure was defined as one or more benzodiazepine prescriptions during the first trimester. We determined the relative risks (RRs) and confidence intervals (CIs) of overall congenital malformations and 12 types of organ-specific malformations. Infants were followed from birth to death or 31 December 2019, whichever came first (up to 8 years of age). Propensity score fine stratification was employed to control for 45 potential confounders. Among a total of 3,094,227 pregnancies, 40,846 (1.3%) were exposed to benzodiazepines during the first trimester (mean [SD] age, 32.4 [4.1] years). The absolute risk of overall malformations was 65.3 per 1,000 pregnancies exposed to benzodiazepines versus 51.4 per 1,000 unexposed pregnancies. The adjusted RR was 1.09 (95% CI 1.05 to 1.13,p< 0.001) for overall malformations and 1.15 (1.10 to 1.21,p< 0.001) for heart defects. Based on mean daily lorazepam-equivalent doses, the adjusted RRs for overall malformations and heart defects were 1.05 (0.99 to 1.12,p= 0.077) and 1.12 (1.04 to 1.21,p= 0.004) for <1 mg/day and 1.26 (1.17 to 1.36,p< 0.001) and 1.31 (1.19 to 1.45,p< 0.001) for >2.5 mg/day doses, respectively, suggesting a dose–response relationship. A small but significant increase in risk for overall and heart defects was detected with several specific agents (range of adjusted RRs: 1.08 to 2.43). The findings were robust across all sensitivity analyses, and negative control analyses revealed a null association. Study limitations include possible exposure misclassification, residual confounding, and restriction to live births.Conclusions: In this large nationwide cohort study, we found that first-trimester benzodiazepine exposure was associated with a small increased risk of overall malformations and heart defects, particularly at the higher daily dose. The absolute risks and population attributable fractions were modest. The benefits of benzodiazepines for their major indications must be considered despite the potential risks; if their use is necessary, the lowest effective dosage should be prescribed to minimize the risk.Trial registration: ClinicalTrials.gov NCT04856436.

Background: Polypharmacy has become a global health problem and is associated with adverse health outcomes in the elderly. This study evaluated the prevalence of polypharmacy and hyper-polypharmacy in elderly patients in South Korea during 2010–2019.Methods: We analyzed the outpatient care of persons aged ≥65 years covered by National Health Insurance (NHI) using NHI claims data from 2010 to 2019. Polypharmacy was defined as the use of ≥5 medications, and hyper-polypharmacy was defined as the use of ≥10 medications, and we examined them over periods of ≥90 days and ≥180 days. The average annual percent change (AAPC) was calculated using Joinpoint statistical software.Results: The prevalence of polypharmacy among ≥90 days of medication use elderly decreased from 42.5% in 2010 to 41.8% in 2019, and the prevalence of hyper-polypharmacy for ≥90 days increased from 10.4% to 14.4%. The prevalence of polypharmacy for ≥180 days increased from 37.8% in 2010 to 38.1% in 2019, and the prevalence of hyper-polypharmacy for ≥180 days increased from 6.4% to 9.4%. The prevalence of polypharmacy for ≥90 days and ≥180 days steadily increased among elderly patients, with AAPCs of 3.7 and 4.5, respectively.Conclusion: The prevalence of polypharmacy for ≥90 days and ≥180 days remained stably high, with rates of about 42 and 38%, respectively, and hyper-polypharmacy increased over the past 10 years in South Korea. Therefore, strategies to address polypharmacy need to be implemented. Further research is also required to identify the clinical outcomes (including mortality risks) associated with polypharmacy.

Inappropriate antibiotic use significantly contributes to antibiotic-resistance, resulting in reduced antibiotic efficacy and increasing physical burden and cost of disease. The goal of this study was to explore antibiotic usage patterns in South Korea using 2007–2014 health insurance claims data. We used the Health Insurance Review & Assessment Service data, which represents nearly the entire population of South Korea, to discern patterns in antibiotic prescribing practices. The daily dose, as defined by the World Health Organization ([defined daily doses]/1000 inhabitants/day, [DID]), was used as a measure of antibiotic use. Subgroup analyses were performed on the basis of patient characteristics (sex, age, and disease) and provider characteristics (type of medical institution). Antibiotic use in DID increased from 23.5 in 2007 to 27.7 in 2014. The ≤ 6 years old age group showed the highest level of usage at 59.21 DID in 2014, and showed an increasing trend each year. DIDs of beta-lactam antibacterials, penicillins (J01C), other beta-lactam antibacterials (J01D), lincosamides and streptogramins (J01F), quinolone antibacterials (J01M), and other antibacterials (J01X) increased over time. This study provides valuable statistics regarding antibiotic usage in South Korea; this is important for guiding health policy with regard to antibiotic usage. There is a need for further study exploring antibiotics use and resistance.

Background: This study aimed to investigate the association between continuous polypharmacy and hospitalization, emergency department (ED) visits, and death.Methods: This retrospective study utilized 6,443,896 patients aged between 65 and 84 years of National Health Insurance claims data from 2016 to 2018. Polypharmacy and excessive polypharmacy were defined as the concurrent use of 5 or more and 10 or more medications, respectively, for durations of both 90 days or more and 180 days or more within a 1-year observation period. The primary outcome measures included all-cause hospitalization, ED visits, and mortality. Multiple logistic regression models were used adjusting for patients’ general characteristics, comorbidities, and history of hospitalization or ED visits.Results: Among 2,693,897 patients aged 65–84 years who had used medicines for 180 days or more (2,955,755 patients taking medicines for 90 days or more), the adverse outcomes were as follows: 20.5% (20.3%) experienced hospitalization, 10.9% (10.8%) visited the ED, and 1% (1%) died, respectively. In patients who exhibited polypharmacy for more than 180 days, the adjusted odds ratio of adverse outcomes was 1.32 (95% confidence interval [CI], 1.31–1.33) for hospitalization, 1.32 (95% CI, 1.31–1.33) for ED visits, 1.63 (95% CI, 1.59–1.67) for death, and that in excessive polypharmacy patients for more than 180 days was 1.85 for hospitalization, 1.92 for ED visits, and 2.57 for death, compared to non-polypharmacy patients.Conclusion: Our results suggest that polypharmacy in older adults might lead to negative health consequences. Thus, interventions to optimize polypharmacy may need to be implemented.

Polypharmacy may cause adverse health outcomes in the elderly. This study examined the prevalence of continuous polypharmacy and hyper‐polypharmacy, factors associated with polypharmacy, and the most frequently prescribed medications among older adults in South Korea. This was a retrospective observational study using National Health Insurance claims data. In total, 7,358,953 Korean elderly patients aged 65 years and older were included. Continuous polypharmacy and hyper‐polypharmacy were defined as the use of ≥5 and ≥10 medications, respectively, for both ≥90 days and ≥180 days within 1 year. A multivariate logistic regression analysis was conducted with adjustment for general characteristics (sex, age, insurance type), comorbidities (12 diseases, number of comorbidities, and Elixhauser Comorbidity Index [ECI] classification), and healthcare service utilization. Among 7.36 million elderly patients, 47.8% and 36.9% had polypharmacy for ≥90 and ≥180 days, and 11.9% and 7.1% of patients exhibited hyper‐polypharmacy for ≥90 and ≥180 days, respectively. Male sex, older age, insurance, comorbidities (cardio‐cerebrovascular disease, diabetes mellitus, depressive disorder, dementia, an ECI score of ≥3), and healthcare service utilization were associated with an increased probability of polypharmacy. The therapeutic class with the most prescriptions was drugs for acid‐related disorders (ATC A02). The number of outpatient visit days more strongly influenced polypharmacy than hospitalizations and ED visits. This study provides health policymakers with important evidence about the critical need to reduce polypharmacy among older adults.