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Abstract Background Previous studies that assessed the risk of cardiovascular outcomes in survivors of coronavirus disease 2019 (COVID-19) were likely limited by lack of generalizability and selection of controls nonrepresentative of a counterfactual situation regarding COVID-19-related hospitalization. This study determined whether COVID-19 hospitalization was associated with incident cardiovascular outcomes compared to non-COVID-19 pneumonia hospitalization. Methods Nationwide population-based study conducted using the Korean National Health Insurance Service database. A cohort of 132,784 inpatients with COVID-19 (October 8, 2020–September 30, 2021) and a cohort of 31,173 inpatients with non-COVID-19 pneumonia (January 1–December 31, 2019) were included. The primary outcome was the major adverse cardiovascular event (MACE; a composite of myocardial infarction and stroke). Hazard ratios (HRs) with 95% confidence intervals (CIs) of all outcomes of interest were estimated between inverse probability of treatment-weighted patients with COVID-19 and non-COVID-19 pneumonia. Results After weighting, the COVID-19 and non-COVID-19 pneumonia groups included 125,810 (mean [SD] age, 47.2 [17.6] years; men, 49.3%) and 28,492 patients (mean [SD] age, 48.6 [18.4] years; men, 47.2%), respectively. COVID-19 hospitalization was not associated with an increased risk of the MACE (HR, 0.84; 95% CI 0.69–1.03). However, the MACE (HR, 7.30; 95% CI 3.29–16.21), dysrhythmia (HR, 1.88; 95% CI 1.04–3.42), acute myocarditis (HR, 11.33; 95% CI 2.97–43.20), myocardial infarction (HR, 6.78; 95% CI 3.03–15.15), congestive heart failure (HR, 1.95; 95% CI 1.37–2.77), and thrombotic disease (HR, 8.26; 95% CI 4.06–16.83) risks were significantly higher in patients with COVID-19 aged 18–39 years. The findings were consistent after adjustment for preexisting cardiovascular disease. COVID-19 hospitalization conferred a higher risk of acute myocarditis (HR, 6.47; 95% CI 2.53–16.52) or deep vein thrombosis (HR, 1.97; 95% CI 1.38–2.80), regardless of vaccination status. Conclusions Hospitalized patients with COVID-19 were not at an increased risk of cardiovascular outcomes compared to patients with non-COVID-19 pneumonia. Further studies are needed to evaluate whether the increased risk of cardiovascular outcomes is confined to younger patients.

Abstract Background Medications influencing the risk of fall-related injuries (FRIs) in older adults have been inconsistent in previous guidelines. This study employed case–control design to assess the association between FRIs and medications, and an additional case-crossover design was conducted to examine the consistency of the associations and the transient effects of the medications on FRIs. Methods This study was conducted using a national claims database (2002–2015) in Korea. Older adults (≥ 65 years) who had their first FRI between 2007 and 2015 were matched with non-cases in 1:2 ratio. Drug exposure was examined for 60 days prior to the date of the first FRI (index date) in the case–control design. The hazard period (1–60 days) and two control periods (121–180 and 181–240 days prior to the index date) were investigated in the case-crossover design. The risk of FRIs with 32 medications was examined using conditional logistic regression after adjusting for other medications that were significant in the univariate analysis. In the case-crossover study, the same conditional model was applied. Results In the case–control design, the five medications associated with the highest risk of FRIs were muscle relaxants (adjusted odd ratio(AOR) = 1.35, 95% confidence interval (CI) = 1.31–1.39), anti-Parkinson agents (AOR = 1.30, 95%CI = 1.19–1.40), opioids (AOR = 1.23, 95%CI = 1.19–1.27), antiepileptics (AOR = 1.19, 95%CI = 1.12–1.26), and antipsychotics (AOR = 1.16, 95%CI = 1.06–1.27). In the case-crossover design, the five medications associated with the highest risk of FRIs were angiotensin II antagonists (AOR = 1.87, 95%CI = 1.77–1.97), antipsychotics (AOR = 1.63, 95%CI = 1.42–1.83), anti-Parkinson agents (AOR = 1.58, 95%CI = 1.32–1.85), muscle relaxants (AOR = 1.42, 95%CI = 1.35–1.48), and opioids (AOR = 1.35, 95%CI = 1.30–1.39). Conclusions Anti-Parkinson agents, opioids, antiepileptics, antipsychotics, antidepressants, hypnotics and sedatives, anxiolytics, muscle relaxants, and NSAIDs/antirheumatic agents increased the risk of FRIs in both designs among older adults. Medications with a significant risk only in the case-crossover analysis, such as antithrombotic agents, calcium channel blockers, angiotensin II antagonists, lipid modifying agents, and benign prostatic hypertrophy agents, may have transient effects on FRIs at the time of initiation. Corticosteroids, which were only associated with risk of FRIs in the case–control analysis, had more of cumulative than transient effects on FRIs.

Abstract Background The concurrent use of anticholinergics and acetylcholinesterase inhibitors (ACHEIs) in Parkinson’s disease (PD) patients with dementia should be avoided because the opposing pharmacological actions of both drugs reduce the treatment efficacy. We aimed to investigate the prevalence of the concurrent use of these two types of drugs in Korean patients. Methods In the 2017 Health Insurance Review and Assessment Service–National Aged Patient Sample data, comprising insurance claims records for a 10% random sample of patients aged ≥ 65 years in Korea, “concurrent use” was defined as the overlapping of anticholinergic and ACHEI doses for at least 2 months. Results Among 8,845 PD patients with dementia, 847 (9.58%) were co-administered anticholinergics, used to treat the motor symptoms of PD, and ACHEIs for a mean duration of 7.7 months. A total of 286 (33.77% of all co-administered) patients used both drug types concurrently all year. About 80% of concurrent users were prescribed each drug by the same prescriber, indicating that coadministration may not be due to a lack of information sharing between providers. Logistic regression analysis showed that patients mainly treated at clinics (odds ratio (OR), 1.541; 95% confidence interval (CI), 1.158–2.059), hospitals (OR, 2.135; 95% CI, 1.586–2.883), and general hospitals (OR, 1.568; 95% CI, 1.221–2.028) were more likely to be co-prescribed anticholinergics and ACHEIs than those mainly treated at tertiary-care hospitals. PD patients with dementia treated at healthcare organizations located in areas other than the capital city had an approximately 22% higher risk of concurrent use (OR: 1.227, 95% CI: 1.046–1.441). Conclusions The concurrent use of anticholinergics for the motor symptoms of PD and ACHEIs in elderly Korean PD patients with dementia cannot be ignored, and strategies that mitigate potentially inappropriate concurrent drug use are required.

Abstract Background Previous randomized trials of vitamin C, hydrocortisone, and thiamine on sepsis were limited by short-term vitamin C administration, heterogeneous populations, and the failure to evaluate each component’s effect. The purpose of this study was to determine whether vitamin C alone for ≥ 5 days or in combination with corticosteroids and/or thiamine was associated with decreased mortality across the sepsis population and subpopulation. Methods Nationwide population-based study conducted using the Korean National Health Insurance Service database. A total of 384,282 adult patients with sepsis who were admitted to the intensive care unit were enrolled from January 2017 to December 2019. The primary outcome was hospital mortality, while the key secondary outcome was 90-day mortality. Results The mean [standard deviation] age was 69.0 [15.4] years; 57% were male; and 36,327 (9%) and 347,955 did and did not receive vitamin C, respectively. After propensity score matching, each group involved 36,327 patients. The hospital mortality was lower by − 0.9% in the treatment group (17.1% vs 18.0%; 95% confidence interval, − 1.3 to − 0.5%; p

Abstract Background The pharmaceutical industry is heavily regulated. Partly for this reason, new drugs generally take over 10 years from the product development stage to market entry. Although regulations affect the pharmaceutical industry over a long period, previous studies investigating the impact of new regulatory policies have usually focused on the short period before and after implementing that policy. Therefore, the purpose of this study is to examine whether and how significantly regulatory policies affect long-term innovation in the pharmaceutical industry in Korea. Methods This study focused on three significant regulatory policies: the introduction of the product patent system, changes in the Good Manufacturing Practice (GMP) system, and the Drug Expenditure Rationalization Plan (DERP). The study used interrupted time series (ITS) analysis to investigate the long-term impacts of the policies before and after implementation. Results Our results show that introducing the product patent system in 1987 significantly increased the number of Korean patent applications. The effect of the revised GMP policies was also statistically significant, both before and after implementation and between pre-emptive companies and non-pre-emptive ones. However, due to the companies' negotiations with the regulatory authorities or the regulatory system that links drug approval and price evaluation, the DERP did not significantly delay new drug registration in Korea. Conclusion This study showed that the policies of the product patent system, GMP policies, and DERP regulations have significantly encouraged pharmaceutical companies to strive to meet regulatory requirements and promote innovation in Korea. The study suggests that it is necessary for companies to pre-emptively respond to systemic changes in development and production strategies to deal with regulatory changes and achieve sustainable growth. Also, our study results indicate that since government policies motivate the innovative system of the pharmaceutical industry, governmental authorities, when formulating pharmaceutical policies, need to consider the impact on the long-term innovation of the industry.

Abstract Background Rapid response systems (RRSs) are essential components of patient safety systems; however, limited evidence exists regarding their effectiveness and optimal structures. We aimed to assess the activation patterns and outcomes of RRS implementation with/without a real-time automatic alerting system (AAS) based on electronic medical records (EMRs). Methods We retrospectively analyzed clinical data of patients for whom the RRS was activated in the surgical wards of a tertiary university hospital. We compared the code rate, in-hospital mortality, unplanned intensive care unit (ICU) admission, and other clinical outcomes before and after applying RRS and AAS as follows: pre-RRS (January 2013–July 2015), RRS without AAS (August 2015–November 2016), and RRS with AAS (December 2016–December 2017). Results In-hospital mortality per 1000 admissions decreased from 15.1 to 12.9 after RRS implementation (p

Abstract Background This study aimed to evaluate the crude incidence rates and relative risk of malignancy in Korean patients with SLE. Methods We conducted a retrospective nationwide cohort study using databases from the National Health Insurance Service in Korea. All prevalent SLE patients aged over 19 were identified from January 2012 to December 2014 and observed until the diagnosis of malignancy, death, or end of the study, December 2015. The crude incidence rates (IRs) and standardised incidence ratios (SIRs) of overall and site-specific malignancies in SLE patients were estimated. Results We identified 17,854 SLE patients and during the observation period (60,511 person-years [PYs]), 768 solid malignancies (126.9/10,000 PYs) and 68 haematologic malignancies (11.2/10,000 PYs) occurred in SLE patients. In SLE patients, breast and reproductive system and thyroid cancers occurred predominantly, followed by liver and colon cancers. The SIRs of overall, solid, and haematologic malignancies of SLE patients compared to the general population were 1.8 (95% confidence interval [CI] 1.6–1.9), 1.7 (95% CI 1.5–1.8), and 5.9 (95% CI 4.8–7.3), respectively. In solid malignancies, head and neck (2.7, 95% CI 1.1–4.2), bladder (2.4, 95% CI 1.1–3.8), liver (1.9, 95% CI 1.4–2.3), pancreas (1.9, 95% CI 1.3–2.6), lung (1.8, 95% CI 1.2–2.4), colon (1.7, 95% CI 1.3–2.2), thyroid (1.6, 95% CI 1.3–1.8) and breast and reproductive system (1.5, 95% CI 1.2–1.7) cancers are at increased risk in SLE patients. Conclusion An increased risk of haematologic and solid malignancies was observed in Korean patients with SLE compared to the general population.

Abstract Background This study investigated the sex-specific incidence of asthma and the effects of modifiable risk factors, particularly obesity, on asthma incidence among middle-aged and older individuals in Korea. Methods We used data from the National Health Insurance Service-Health Screening Cohort (NHIS-HEALS), which includes health examinees aged 40–79 years in 2002–2003. In total, 459,529 participants with baseline anthropometric measurements were followed-up for 10 years and the development of asthma was evaluated (2004–2013). For subgroup analysis, 246,019 participants who had body mass index (BMI) and waist circumference (WC) measurements taken in 2008–2009 were included in the analysis of the asthma incidence for 2010–2013. Factors associated with asthma were analysed using Cox proportional hazard models. Results The cohort comprised 4,248,813 (men, 2,358,541; women, 1,890,272) person-years of follow-up for 2004–2013. The asthma incidence was 10.58 and 15.03 per 1000 person-years for men and women, respectively. Asthma incidence increased with age, notably so in men. Obesity based on the baseline BMI was significantly associated with asthma development in both sexes (men, HR = 1.23, 95% confidence interval (CI) = 1.13–1.34; women, HR = 1.40 95% CI = 1.32–1.48). High WC was also related to asthma incidence in both sexes with statistical significance (men, HR = 1.34, 95% CI = 1.16–1.57; women, HR = 1.19 95% CI = 1.03–1.37). Analysis of the combined effects of BMI and WC showed that men had a higher asthma risk in the group with both general obesity and abdominal obesity than in the group with non-abdominal obesity and normal BMI. However, obese women had a higher risk of asthma regardless of abdominal obesity. Similarly, smoking was associated with asthma in both sexes but drinking and physical activity showed different associations between the sexes. Conclusions Our results revealed that asthma incidence was substantially high at old age and lifestyle factors were associated with asthma development. Practical strategies including weight control and healthy lifestyle modification are required to prevent asthma in older people.

Abstract Objective To examine factors related to the use of opioids as an early treatment option for knee OA patients Methods Using the Korean nationwide claim database, we selected knee OA patients between 2013 and 2015. Among them, patients without any claim of knee OA for 2 years before the index date were included as our study population. We analyzed their first claim for prescriptions, including tramadol and stronger opioids, at the index date of each patient. Using a multinomial model, we identified factors associated with the early use of tramadol and stronger opioids in knee OA patients. Results Among a total of 2,857,999 knee OA patients, 12.2% (n = 348,516) were treated with opioids as their first treatment. However, the prevalence of stronger opioid use was only 0.07% (n = 1972). Male sex (OR 1.28 in tramadol, OR 1.13 in stronger opioids) and comorbidities with depression (OR 1.05, 1.46), low back pain (OR 1.13, 1.30), intervertebral disc disorder (OR 1.11, 1.40), and spinal stenosis (OR 1.27, 1.55) were the factors for the early use of tramadol or stronger opioids in knee OA patients. Patients in a tertiary referral hospital tended to use tramadol or stronger opioids than those in clinics (OR 1.04, 56.63, respectively). Conclusion In Korea, 12.2% of knee OA patients were treated with opioids as an early treatment, and tramadol was used more commonly than stronger opioids. Male sex and having comorbidities such as depression or musculoskeletal disease are patient factors associated with the early use of opioids in knee OA patients.

Abstract Background Histologic grade is the most important predictor of the clinical outcome of non-muscle invasive (Ta, T1) papillary urothelial carcinoma (NMIPUCa), but its ambiguous criteria diminish its power to predict recurrence/progression for individual patients. We attempted to find an objective and reproducible histologic predictor of NMIPUCa that correlates well with the clinical outcome. Methods A total of 296 PUCas were collected from the Departments of Surgical Pathology of 11 institutions in South Korea. The clinical outcome was grouped into no event (NE), recurrence (R), and progression (P) categories. All 25 histological parameters were numerically redefined. The clinical pathology of each case was reviewed individually by 11 pathologists from 11 institutions based on the 2004 WHO criteria and afterwards blindly evaluated by two participants, based on our proposed parameters. Univariate and multivariate logistic regression analyses were performed using the R software package. Results The level of mitoses was the most reliable parameter for predicting the clinical outcome. We propose a four-tiered grading system based on mitotic count (> 10/10 high-power fields), nuclear pleomorphism (smallest-to-largest ratio of tumor nuclei >20), presence of divergent histology, and capillary proliferation (> 20 capillary lumina per papillary core). Conclusions The level of mitoses at the initial bladder biopsy and transurethral resection (TUR) specimen appeared to be an independent predictor of the Ta PUCa outcome. Other parameters include the number of mitoses, nuclear pleomorphism, divergent histology, and capillary proliferation within the fibrovascular core. These findings may improve selection of patients for a therapeutic strategy as compared to previous grading systems.