Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and the risk of hepatocellular carcinoma: a nationwide cohort study.

Background/Aims: To determine the association between evolutionary changes in metabolic dysfunction-associated steatotic liver disease (MASLD) status and the risk of hepatocellular carcinoma (HCC) in a nationwide population-based cohort. Methods: Information on study participants were derived from the Korea National Health Insurance Service database. The study population consisted of 5,080,410 participants who underwent two consecutive biennial health screenings between 2009 and 2012. All participants were followed up until HCC, death, or 31 December 2020. Association of evolutionary changes in MASLD status as assessed by fatty liver index and cardiometabolic risk factors, including persistent non-MASLD, resolved MASLD, incident MASLD, and persistent MASLD, with HCC risk was evaluated using the multivariable-adjusted Cox proportional hazards regression. Results: Among the 5,080,410 participants with 39,910,331 person-years of follow-up, 4,801 participants developed HCC. The incidence of HCC in participants with resolved, incident, and persistent MASLD was approximately 2.2-, 2.3-, and 4.7-fold higher, respectively, than that in those with persistent non-MASLD among the Korean adult population. When stratifying the participants according to the evolutionary change in MASLD status, persistent (adjusted hazard ratio [aHR], 2.94; 95% confidence interval [CI], 2.68-3.21; P<0.001), incident (aHR, 1.85; 95% CI, 1.63-2.10; P<0.001), and resolved MASLD (aHR, 1.33; 95% CI, 1.18-1.50; P<0.001) had an increased risk of HCC than that of persistent non-MASLD. Conclusions: The evolutionary changes in MASLD were associated with the differential risk of HCC independent of metabolic risk factors and concomitant medications, providing additional information on the risk of HCC stratification in patients with MASLD.

Association of balance impairment with risk of incident cardiovascular diseases among older adults.

BACKGROUND: Rapid decline in balance is a hallmark of aging, elevating the risk of falls and other age-related geriatric illnesses among older adults. OBJECTIVE: Our aim was to assess whether impairment in balance function is associated with the risk of incident CVD in older adults. DESIGN: Retrospective cohort analysis. PARTICIPANTS: A total of 129,024 participants who had undergone health screening between 2002 and 2009 were derived from the National Health Insurance Service-Senior cohort. MAIN MEASURES: Balance impairment was evaluated using the open-eyes one-leg standing (OLS) test. The association between balance impairment and incident CVD was analyzed using the Cox proportional hazards regression model. All participants were followed up with until either the date of the first incident of CVD, death, or 31 December 2019. KEY RESULTS: Those with abnormal balance function (< 10 s in OLS test) had a higher risk of CVD (adjusted hazard ratio [aHR] 1.23, CI 1.16-1.31). The association was significant in both the obese and the non-obese, but it seemed to be more pronounced in the latter. Results were supported by sensitivity analyses that did not include cases of CVD development in the first 1, 2, or 3 years and that used a different criterion to define balance dysfunction (< 9 s in OLS test). CONCLUSIONS: Older adults with balance impairment were found to have an increased risk of incident CVD. Patients with impaired balance function may be a high-risk population who require preventive managements against CVD.

Risk of Bell's palsy following SARS-CoV-2 infection: a nationwide cohort study.

OBJECTIVES: Despite some evidence of an increased risk of neurologic symptoms following viral vector COVID-19 vaccine administration, it is unclear whether SARS-CoV-2 infection is associated with Bell's palsy (BP), especially over a long enough follow-up period. METHODS: The study population of this nationwide population-based study was derived from the South Korean population, including 11 593 365 and 36 565 099 participants with and without COVID-19, respectively. The Fine and Gray's regression model was utilized to calculate the adjusted subdistribution hazard ratio (aSHR), considering death as a competing risk, to assess the association between SARS-CoV-2 infection and the risk of BP. All participants were followed up from 1 December 2021, until the incident BP, SARS-CoV-2 infection, death, or 31 March 2022. Subgroup analyses were conducted based on participants' vaccination status (completion of the primary series vs. unvaccinated). RESULTS: COVID-19 was associated with an increased risk of BP in all participants (aSHR, 1.24; CI, 1.19-1.29). However, the size of the COVID-19-related BP risk was significantly lower among those who completed the primary series of the COVID-19 vaccine (aSHR, 1.20; 95% CI, 1.15-1.25) compared to those who were unvaccinated (aSHR, 1.84; 95% CI, 1.59-2.12; p for interaction: <0.001). The severity of COVID-19 exhibited a gradual escalation in BP risk for both vaccinated and unvaccinated individuals. DISCUSSION: While both unvaccinated individuals and those who completed the primary series of the COVID-19 vaccine may be at an increased risk of developing BP due to COVID-19, the risk appears to be lower among those who completed the vaccination.

Exercise Frequency Reduction Is Associated With Higher Risk of Infection in Newly Diagnosed Diabetes: A Nationally Representative Cohort Study.

BACKGROUND: Exercise is an important method to control the progression of diabetes. Since diabetes compromises immune function and increases the risk of infectious diseases, we hypothesized that exercise may affect the risk of infection by its immunoprotective effects. However, population-based cohort studies regarding the association between exercise and the risk of infection are limited, especially regarding changes in exercise frequency. The aim of this study was to determine the association between the change in exercise frequency and the risk of infection among patients with newly diagnosed diabetes. METHODS: Data of 10,023 patients with newly diagnosed diabetes were extracted from the Korean National Health Insurance Service-Health Screening Cohort. Self-reported questionnaires for moderate-to-vigorous physical activity (MVPA) were used to classify changes in exercise frequency between two consecutive two-year periods of health screenings (2009-2010 and 2011-2012). The association between changes in exercise frequency and the risk of infection was evaluated using multivariable Cox proportional-hazards regression. RESULTS: Compared with engaging in ≥ 5 times of MVPA/week during both periods, a radical decrease in MVPA (from ≥ 5 times of MVPA/week to physical inactivity) was associated with a higher risk of pneumonia (adjusted hazard ratio [aHR], 1.60; 95% confidence interval [CI], 1.03-2.48) and upper respiratory tract infection (aHR, 1.15; 95% CI, 1.01-1.31). In addition, a reduction of MVPA from ≥ 5 to < 5 times of MVPA/week was associated with a higher risk of pneumonia (aHR, 1.52; 95% CI, 1.02-2.27), whereas the risk of upper respiratory tract infection was not higher. CONCLUSION: Among patients with newly diagnosed diabetes, a reduction in exercise frequency was related to an increase in the risk of pneumonia. For patients with diabetes, a modest level of physical activity may need to be maintained to reduce the risk of pneumonia.

Inverse association between changes in systolic and diastolic blood pressure and risk of depression: A nationally representative cohort study.

BACKGROUND: Depression is one of complex mental disorders with diverse etiological factors but the association between blood pressure (BP) and depression is unknown. We aimed to investigate the association between changes in BP (systolic and diastolic) and incident depression. METHODS: From the National Health Insurance Service-Health Screening Cohort (NHIS-HEALS), 224,192 participants who underwent biennial health screenings from period I (2004-05) and II (2006-07) were included in the study. Systolic BP (SBP) and diastolic BP (DBP) categories were defined as follows: SBP into 5 categories (<90 mmHg, 90 mmHg -119 mmHg, 120 mmHg -129 mmHg, 130 mmHg -139 mmHg, ≥140 mmHg) and DBP into 4 categories (<60 mmHg, 60 mmHg -79 mmHg, 80 mmHg -89 mmHg, ≥90 mmHg). Also, BP levels were classified into 5 groups: normal, elevated BP, stage 1 BP, stage 2 BP, hypotension. Using the Cox proportional hazards regression, changes in SBP and DBP between two screening periods and the risk of depression were calculated by adjusted hazard ratio (aHR) and 95 % confidence interval (CI). RESULTS: There were 17,780 depression events during 1.5 million person-year of follow-up. Compared to the participants with SBP ≥ 140 mmHg or DBP ≥ 90 mmHg from both periods, those who decreased SBP from ≥140 mmHg to 120 mmHg-129 mmHg (aHR 1.13; 95 % CI 1.04-1.24; P = 0.001) and those who decreased DBP from ≥90 mmHg to 60 mmHg-79 mmHg (aHR 1.10; 95 % CI 1.02-1.20; P = 0.020) showed a higher risk of depression, respectively. CONCLUSIONS: Changes in SBP and DBP showed an inverse relationship with depression risk.

Safety of COVID-19 Vaccines among Patients with Type 2 Diabetes Mellitus: Real-World Data Analysis.

BACKGROUND: Little is known about the adverse events (AEs) associated with coronavirus disease 2019 (COVID-19) vaccination in patients with type 2 diabetes mellitus (T2DM). METHODS: This study used vaccine AE reporting system data to investigate severe AEs among vaccinated patients with T2DM. A natural language processing algorithm was applied to identify people with and without diabetes. After 1:3 matching, we collected data for 6,829 patients with T2DM and 20,487 healthy controls. Multiple logistic regression analysis was used to calculate the odds ratio for severe AEs. RESULTS: After COVID-19 vaccination, patients with T2DM were more likely to experience eight severe AEs than controls: cerebral venous sinus thrombosis, encephalitis myelitis encephalomyelitis, Bell's palsy, lymphadenopathy, ischemic stroke, deep vein thrombosis (DVT), thrombocytopenia (TP), and pulmonary embolism (PE). Moreover, patients with T2DM vaccinated with BNT162b2 and mRNA-1273 were more vulnerable to DVT and TP than those vaccinated with JNJ-78436735. Among patients with T2DM administered mRNA vaccines, mRNA-1273 was safer than BNT162b2 in terms of the risk of DVT and PE. CONCLUSION: Careful monitoring of severe AEs in patients with T2DM may be necessary, especially for those related to thrombotic events and neurological dysfunctions after COVID-19 vaccination.

Changes in high-density lipoprotein cholesterol with risk of Cardiovascular Disease among initially high-density lipoprotein-high participants.

BACKGROUND: High-density lipoprotein cholesterol's (HDL-C) long-held status as a cardiovascular disease (CVD) preventative has been called into question. Most of the evidence, however, focused on either the risk of death from CVD, or on single time point level of HDL-C. This study aimed to determine the association between changes in HDL-C levels and incident CVD in individuals with high baseline HDL-C levels (≥ 60 mg/dL). METHODS: 77,134 people from the Korea National Health Insurance Service-Health Screening Cohort were followed for 517,515 person-years. Cox proportional hazards regression was used to evaluate the association between change in HDL-C levels and the risk of incident CVD. All participants were followed up until 31 December 2019, CVD, or death. RESULTS: Participants with the greatest increase in their HDL-C levels had higher risks of CVD (adjusted hazard ratio [aHR], 1.15; 95% confidence interval [CI], 1.05-1.25) and CHD (aHR 1.27, CI 1.11-1.46) after adjusting for age, sex, household income, body mass index, hypertension, diabetes mellitus, dyslipidemia, smoking, alcohol consumption, moderate-to-vigorous physical activity, Charlson comorbidity index, and total cholesterol than those with the lowest increase in HDL-C levels. Such association remained significant even among participants with decreased low-density lipoprotein cholesterol (LDL-C) levels for CHD (aHR 1.26, CI 1.03-1.53). CONCLUSIONS: In people with already high HDL-C levels, additional increases in HDL-C levels may be associated with an increased risk of CVD. This finding held true irrespective of the change in their LDL-C levels. Increasing HDL-C levels may lead to unintentionally elevated risk of CVD.

Association Between Hearing Impairment and Incident Depression: A Nationwide Follow-up Study.

BACKGROUND: Accumulating evidence suggests that hearing impairment is associated with the onset of depression. However, large-scale epidemiological studies are required to define this association more clearly. We aimed to investigate the risk of new-onset depression in Korean older adults with and without hearing impairment. METHODS: From the National Health Insurance Service-Senior Cohort, which is a retrospective-prospective hybrid database, we analyzed data for 254,466 older adults enrolled in the Korea National Health Insurance Service-Senior Cohort who underwent at least one health screening between 2003 and 2019. A Cox proportional hazards regression model was used to evaluate the association between hearing impairment and the risk of incident depression, which was presented as adjusted hazard ratios (aHR) with 95% confidence intervals (CIs). All participants were followed up until the date of incident depression, death, or December 31, 2019. RESULTS: During 3,417,682 person-years of follow-up investigation, hearing impairment was associated with a higher risk of incident depression (vs. no hearing impairment) in the final adjusted model (aHR, 1.11; 95% CI, 1.01-1.21; p = 0.033). Stratified analyses revealed a significant interaction among age, hearing impairment, and the risk of depression. Participants aged <65 years had a higher risk of depression (aHR, 1.29; 95% CI, 1.12-1.50; p < 0.001) than those aged 65 or above (aHR, 1.15; 95% CI, 1.01-1.30; p = 0.032). CONCLUSIONS: Hearing impairment is independently associated with a higher risk of depression among older adults. The prevention and treatment of hearing impairment may aid in mitigating the risk of incident depression. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 133:3144-3151, 2023.

Development and validation of a nonalcoholic fatty liver disease-based self-diagnosis tool for diabetes.

Background: Prediction of type 2 diabetes mellitus (DM) has been studied widely. However, a hospital visit was necessary to apply previous prediction models for the evaluation of DM. This study was conducted to develop and validate a hospital visit-free self-diagnosis tool for DM. Methods: Participants who underwent health screening between 2017-2018 (n=7,519; training cohort) and 2019-2020 (n=7,564; validation cohort) were extracted from the Korea National Health and Nutrition Examination Survey (KNHANES). DM was defined as doctor-diagnosed DM in a questionnaire. Logistic regression was used to determine independent predictors for DM, and a multivariable logistic regression-based nomogram was developed for the prediction of DM, which was validated in a cohort consisting of an independent population. The presence of nonalcoholic fatty liver disease (NAFLD) was operationally defined using the KNHANES-NAFLD score. Results: Age, sex, waist circumference, systolic blood pressure, total cholesterol, triglyceride, aspartate aminotransferase, blood urea nitrogen, urinary protein, urinary glucose, and NAFLD were identified as independent predictors for DM. After excluding laboratory variables that require laboratory tests, a simplified multivariable model was conducted based on hospital visit-free variables, including age, sex, waist circumference, systolic blood pressure, and NAFLD. The full and simplified prediction models for DM were presented as nomograms. In the independent validation cohort, the full and simplified DM prediction models were validated with an area under the curve values of 0.903 and 0.824 from the receiver operating characteristic curves, respectively. Conclusions: Involvement of NAFLD has allowed satisfactory prediction of DM without laboratory tests that require a hospital visit. The developed model may be promising in terms of early diagnosis of DM among individuals without hospital visits and may reduce the socioeconomic burden of DM in the real-world, which awaits future prospective trials to confirm.

Association between visit-to-visit fasting glycemic variability and depression: a retrospective cohort study in a representative Korean population without diabetes.

Glycemic variability (GV) is a risk factor for depression in patients with diabetes. However, whether it is also a predictor of incident depression in people without diabetes remains unclear. We aimed to investigate the association between visit-to-visit variability in fasting serum glucose (FSG) levels and the incidence of depression among Koreans without diabetes. This retrospective cohort study included data of people without diabetes who did not have depression at baseline and had at least three FSG measurements (n = 264,480) extracted from the 2002-2007 Korean National Health Insurance Service-National Health Screening Cohort. GV was calculated as the average successive variability of FSG. Among 264,480 participants, 198,267 were observed during 2008-2013 and their hazard ratios (HR) of incident depression were calculated. Participants with the highest GV showed a higher risk of depression in fully adjusted models than those with the lowest GV (HR, 1.09; 95% CI, 1.02-1.16). The risk of incident depression heightened with increasing GV (p for trend < 0.001). Greater visit-to-visit GV may be associated with the risk of developing depression in people without diabetes. Conversely, maintaining steady FSG levels may reduce the risk of incident depression in people without diabetes.

Health-Screening-Based Chronic Obstructive Pulmonary Disease and Its Effect on Cardiovascular Disease Risk.

Chronic obstructive pulmonary disease (COPD) is considered a major cause of death worldwide, and various studies have been conducted for its early diagnosis. Our work developed a scoring system by predicting and validating COPD and performed predictive model implementations. Participants who underwent a health screening between 2017 and 2020 were extracted from the Korea National Health and Nutrition Examination Survey (KNHANES) database. COPD individuals were defined as aged 40 years or older with prebronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC < 0.7). The logistic regression model was performed, and the C-index was used for variable selection. Receiver operating characteristic (ROC) curves with area under the curve (AUC) values were generated for evaluation. Age, sex, waist circumference and diastolic blood pressure were used to predict COPD and to develop a COPD score based on a multivariable model. A simplified model for COPD was validated with an AUC value of 0.780 from the ROC curves. In addition, we evaluated the association of the derived score with cardiovascular disease (CVD). COPD scores showed significant performance in COPD prediction. The developed score also showed a good effect on the diagnostic ability for CVD risk. In the future, studies comparing the diagnostic accuracy of the derived scores with standard diagnostic tests are needed.

Effects of meteorological factors and air pollutants on the incidence of COVID-19 in South Korea.

Air pollution and meteorological factors can exacerbate susceptibility to respiratory viral infections. To establish appropriate prevention and intervention strategies, it is important to determine whether these factors affect the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, this study examined the effects of sunshine, temperature, wind, and air pollutants including sulfur dioxide (SO2), carbon monoxide (CO), ozone (O3), nitrogen dioxide (NO2), particulate matter ≤2.5 µm (PM2.5), and particulate matter ≤10 µm (PM10) on the age-standardized incidence ratio of coronavirus disease (COVID-19) in South Korea between January 2020 and April 2020. Propensity score weighting was used to randomly select observations into groups according to whether the case was cluster-related, to reduce selection bias. Multivariable logistic regression analyses were used to identify factors associated with COVID-19 incidence. Age 60 years or over (odds ratio [OR], 1.29; 95% CI, 1.24-1.35), exposure to ambient air pollutants, especially SO2 (OR, 5.19; 95% CI, 1.13-23.9) and CO (OR, 1.17; 95% CI, 1.07-1.27), and non-cluster infection (OR, 1.28; 95% CI, 1.24-1.32) were associated with SARS-CoV-2 infection. To manage and control COVID-19 effectively, further studies are warranted to confirm these findings and to develop appropriate guidelines to minimize SARS-CoV-2 transmission.

The Partner Switching System of the SigF Sigma Factor in Mycobacterium smegmatis and Induction of the SigF Regulon Under Respiration-Inhibitory Conditions.

The partner switching system (PSS) of the SigF regulatory pathway in Mycobacterium smegmatis has been previously demonstrated to include the anti-sigma factor RsbW (MSMEG_1803) and two anti-sigma factor antagonists RsfA and RsfB. In this study, we further characterized two additional RsbW homologs and revealed the distinct roles of three RsbW homologs [RsbW1 (MSMEG_1803), RsbW2 (MSMEG_6129), and RsbW3 (MSMEG_1787)] in the SigF PSS. RsbW1 and RsbW2 serve as the anti-sigma factor of SigF and the protein kinase phosphorylating RsfB, respectively, while RsbW3 functions as an anti-SigF antagonist through its protein interaction with RsbW1. Using relevant mutant strains, RsfB was demonstrated to be the major anti-SigF antagonist in M. smegmatis. The phosphorylation state of Ser-63 was shown to determine the functionality of RsfB as an anti-SigF antagonist. RsbW2 was demonstrated to be the only protein kinase that phosphorylates RsfB in M. smegmatis. Phosphorylation of Ser-63 inactivates RsfB to render it unable to interact with RsbW1. Our comparative RNA sequencing analysis of the wild-type strain of M. smegmatis and its isogenic Δaa 3 mutant strain lacking the aa 3 cytochrome c oxidase of the respiratory electron transport chain revealed that expression of the SigF regulon is strongly induced under respiration-inhibitory conditions in an RsfB-dependent way.

Benzodiazepine-Related Cognitive Impairment or Dementia: A Signal Detection Study Using a Case/Non-Case Approach.

OBJECTIVE: The association between benzodiazepine use and the risk of cognitive impairment or dementia has been controversial. Our study aims to detect this association through a case/non-case method using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD) between 2007 and 2016. METHODS: Cases were adverse event (AE)-pairs with suspected cognitive impairment or dementia. 10 non-cases were matched to each case on age and sex. Exposure was defined as use of benzodiazepines, including long-, intermediate-, and short-acting benzodiazepine. We conducted multivariable logistic regression analyses to estimate reporting odds ratios (ROR) and 95% confidence intervals (CI). RESULTS: Of the 1,086,584 AE-pairs, 887 cases were suspected AE-pairs of cognitive impairment or dementia, and 775,444 non-cases were selected. Benzodiazepine use was associated with increased AE-pairs of cognitive impairment or dementia when assessed using those with certain, probable, and/or possible in causality assessments (ROR=2.69, 95% CI=1.66-4.38). Higher ROR estimates were shown in female (2.33, 1.48-3.67) and in those with polypharmacy (2.20, 1.35-3.57). Dementia safety profiles were inconsistent across individual benzodiazepine components. CONCLUSION: These results suggest the potentially increased association between benzodiazepine use and cognitive impairment or dementia in female and those with polypharmacy. Inconsistent safety profiles of benzodiazepine components should be further investigated.

The Multi-Institutional Health Screening Records Database of South Korea: Description and Evaluation of Its Characteristics.

This study sought to describe and to evaluate the characteristics of the Health Screening Records Database (HSRD) of the Korea Association of Health Promotion as a data source for epidemiologic studies. The HSRD was compared to a National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) database for 2015. Common variables between the databases were selected, and sex-based analyses were conducted. The HSRD showed statistical concordance when NHIS-HEALS estimates fell within the HSRD estimate's 95% confidence interval. The HSRD and NHIS-HEALS included 946461 and 111690 participants in health screening programs, respectively. Compared to the NHIS-HEALS, the HSRD had more female (55.2% vs. 42.6%) but fewer older adult participants (34.4% vs. 51.2%). Virtually all variables had clinical concordance, with some having statistical concordance as well, among both general and life-transition program participants. The HSRD comprised more clinical information over a wider age range in contrast to the NHIS-HEALS, while showing clinical concordance. Providing more comprehensive clinical data, the HSRD may serve as an alternative resource for epidemiologic studies.

Signal detection of human papillomavirus vaccines using the Korea Adverse Events Reporting System database, between 2005 and 2016.

Background Adverse events (AEs) not listed on drug labels have recently been reported in young girls vaccinated against HPV, but signal detection related to the human papillomavirus (HPV) vaccine has never been conducted in South Korea using the Korea Adverse Event Reporting System database of Korea Institute of Drug Safety & Risk Management at Ministry of Food and Drug Safety. Objective To analyze signals associated with HPV vaccines using the Korean spontaneous AEs reporting system and data-mining methods and compare the results to current vaccine label information in South Korea and the United States of America, United Kingdom, European Union, and Japan to detect signals not currently listed on the labels. Setting We evaluated the Korea Institute of Drug Safety & Risk Management database from January 2005 to December 2016. After pre-screening the data, the adjusted total numbers of HPV-related AE reports and AEs were 2566 and 4748 and those of all other vaccine-related AE reports and AEs were 21,878 and 120,688, respectively. Methods Three data mining algorithms (proportional reporting ratio, reporting odds ratio and information component) were used to assess AEs. A signal was defined when the criteria for all three indicators were satisfied. The detected signals were compared to the label information of HPV vaccines from South Korea, the United States of America, United Kingdom, European Union, and Japan. Main outcome measure Signals of AE after HPV vaccination, which met all three data mining indices. Results In this study, we found a total 97 signals of AE after HPV vaccination. Of these, 78 AEs were already present on the HPV vaccine labels of South Korea and the following 19 AEs were not listed: neuralgia, tremor, neuritis, depersonalization, axillary pain, personality disorder, increased salivation, peptic ulcer, circulatory failure, hypotension, peripheral ischemia, cerebral hemorrhage, micturition disorder, facial edema, ovarian cyst, weight increase, pain anxiety, oral edema, and back pain. Moreover, AE information on the current HPV vaccine labels of South Korea, the United States of America, United Kingdom, European Union, and Japan was inconsistent. When comparing the 19 AE signals that were not listed on the drug label in South Korea with the labels from the other countries, neuritis, axillary pain, cerebral hemorrhage, facial edema, pain anxiety, and back pain appreared on the U.S. Food and Drug Administration HPV vaccine labels but not on the United Kingdom labels, and hypotension was listed only on labels in the European Union and Japan. Conclusions South Korea should develop a system for proactively updating HPV labels. These results also suggest potential research directions such as vaccination label expansion, pharmacovigilance studies, and identification of causality in AEs associated with HPV vaccination.

Characteristics and trends of spontaneous reporting of therapeutic ineffectiveness in South Korea from 2000 to 2016.

Therapeutic ineffectiveness involves drug-related therapeutic failure, inefficacy or resistance and has not been sufficiently studied. Objective of our study was to evaluate reporting trends in therapeutic ineffectiveness by year and describe factors affecting therapeutic ineffectiveness using the Korea Adverse Event Reporting System. Proportion of therapeutic ineffectiveness reports was based on total submitted reports between 2000 and 2016. Utilizing 2016 alone, we compared the characteristics of therapeutic ineffectiveness with age group and gender matching by random extraction. We conducted a logistic regression analysis to estimate reporting odds ratios (ROR) and its 95% confidence intervals (CI) for reports by type of reporters, e.g., doctors, pharmacists, or consumers. We presented most frequent reports by the anatomical main groups and therapeutic subgroups according to the Anatomical Therapeutic Chemical (ATC) classification system. For the 17-years, the proportion of therapeutic ineffectiveness adverse drug reactions reporting ranged from 0.0% to 3.7% between 2000 and 2016. Of 228,939 reports, 2,797 (1.2%) were submitted in 2016. Consumers accounted for 6.92% of reports and doctors accounted for 45.49%, in which, consumers were more likely to report therapeutic ineffectiveness than doctors (adjusted ROR 3.98; 95% CI, 2.92 to 5.41). According to the ATC classification system, "nervous system" was the most frequently reported anatomical group (18.7%) and "parathyroid hormones and analogues" was reported most frequently in the pharmacological subgroup (23.7%). Teriparatide, a drug used to treat osteoporosis, had the most reports (11.0%). Therapeutic ineffectiveness reports may be used as a scientific tool for the reevaluation of respective drugs in order to confirm of its therapeutic effects.

Differential completeness of spontaneous adverse event reports among hospitals/clinics, pharmacies, consumers, and pharmaceutical companies in South Korea.

The differential pattern and characteristics of completeness in adverse event (AE) reports generated by hospitals/clinics, pharmacies, consumer and pharmaceutical companies remain unknown. Thus, we identified the characteristics of complete AE reports, compared with those of incomplete AE reports, using a completeness score. We used Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System Database (KIDS-KD) between January 1, 2016 and December 31, 2016. The completeness score was determined out of a total of 100 points, based on the presence of information on temporal relationships, age and sex of patients, AE progress, name of reported medication, reporting group by profession, causality assessment, and informational text. AE reports were organized into four groups based on affiliation: hospitals/clinics, pharmacies, consumers, and pharmaceutical companies. Affiliations that had median completeness scores greater than 80 points were classified as 'well-documented' and these reports were further analyzed by logistic regression to estimate the adjusted odds ratios and 95% confidence intervals. We examined 228,848 individual reports and 735,745 drug-AE combinations. The median values of the completeness scores were the highest for hospitals/clinics (95 points), followed by those for consumers (85), pharmacies (75), and manufacturers (72). Reports with causality assessment of 'certain', 'probable', or 'possible' were more likely to be 'well-documented' than reports that had causality assessments of 'unlikely'. Serious reports of AEs were positively associated with 'well-documented' reports and negatively associated with hospitals/clinics.