Regulatory Framework for Drug-Device Combination Products in the United States, Europe, and Korea.

Combination products (CPs) combine two or more product types such as drugs, devices, and/or biological products for increased safety and clinical effectiveness. The emergence of innovative CPs poses new challenges for regulatory agencies in assigning jurisdiction for premarket review and oversight. In US, the 1990 Safe Medical Devices Act defines and provides classification criteria for CPs, and the US government has developed a regulatory process through multiple acts, including the 21st Century Cures Act of 2016. Meanwhile, regulators in the European Union (EU) and the Republic of Korea have recently recognized the importance of premarket pathways for CPs. The European Medicines Agency (EMA) has issued guidelines and explanations on compliance issues related to drug-device CPs under MDR. EMA doesn't have the definitions of CPs, but uses the term drug-device combination products (drug-device CPs). CPs are categorized as drugs or medical devices, which follow their relevant regulatory framework. The Ministry of Food and Drug Safety (MFDS) in Korea has legal definitions of CPs under the Notice of the MFDS. CPs are designated as drugs or medical devices according to their primary mode of actions (PMOA) and follow regulatory processes through the framework of drugs or medical devices. This study aims to comprehensively summarize the regulatory oversight of CPs by analyzing the regulatory policies and legal frameworks in the US, the EU, and Korea. The regulatory challenges encountered when developing CPs are also discussed. With specific emphasis on the combination of drugs and devices, this study provides in-depth insights into the regulatory landscape, shedding light on the unique challenges associated with the development of CPs for this particular intersection of drugs and devices.

Investigating the Connection between Chronic Periodontitis and Parkinson's Disease: Findings from a Korean National Cohort Study.

Recent research suggests a potential relevance between chronic periodontitis (CP) and Parkinson's disease (PD), raising concerns about comorbid PD among elderly CP patients. However, the epidemiologic basis for this association remains unclear. Employing a nested case-control design, this study explored the association between CP and subsequent PD occurrences in Korean adults, leveraging a validated national population-based dataset covering the period from 2002 to 2019. It included 8794 PD patients and 35,176 matched control individuals, established through propensity score matching for age, sex, residential area, and income. Baseline characteristics were compared using standardized differences, and logistic regression was employed to assess the impact of CP histories on PD likelihood while controlling for covariates. We performed a thorough examination of CP events within both 1-year and 2-year intervals preceding the index date, incorporating subgroup analyses. Our analysis revealed no statistically significant association between CP history and PD development overall. However, subgroup analysis revealed a slightly increased likelihood of PD development among CP individuals with a high disease burden (Charlson Comorbidity Index score ≥ 2). In conclusion, although our study did not find a significant overall association between CP history and PD development, the elevated likelihood of PD in subgroups with high disease burden may suggest that comorbidities influence PD probability among certain CP patients. Considering comorbid conditions in PD screening for some individuals with CP may be also important.

Associations between Peritonsillar Abscess and Deep Neck Infection in Chronic Periodontitis Patients: Two Nested Case-Control Studies Using a National Health Screening Cohort.

Background/Introduction: Odontogenic infection is one of the main etiologies of deep neck infection (DNI). However, the relationship between chronic periodontitis (CP) and the incidence of DNI has not been examined. This study aimed to evaluate the incidence of DNI and peritonsillar abscess (PTA) after CP. Methods: The Korean National Health Insurance Service-National Sample Cohort 2002-2019 was used. In Study I, 4585 PTA patients were matched with 19,340 control I participants. A previous history of CP for 1 year was collected, and the odds ratios (ORs) of CP for PTA were analyzed using conditional logistic regression. In Study II, 46,293 DNI patients and 185,172 control II participants were matched. A previous history of CP for 1 year was collected, and conditional logistic regression was conducted for the ORs of CP for DNI. Secondary analyses were conducted in demographic, socioeconomic, and comorbidity subgroups. Results: In Study I, a history of CP was not related to the incidence of PTA (adjusted OR = 1.28, 95% confidence interval [CI] = 0.91-1.81). In Study II, the incidence of DNI was greater in participants with a history of CP (adjusted OR = 1.55, 95% CI = 1.41-1.71). The relationship between CP history and DNI was greater in groups with young, male, low-income, and rural residents. Conclusions: A prior history of CP was associated with a high incidence of DNI in the general population of Korea. Patients with CP need to be managed for the potential risk of DNI.

Association between Gout and Gastric Cancer: A Nested Case-Control Study Using a National Health Sample Cohort.

Given the global significance of gout and gastric cancer (GC) as major health problems with interrelated impacts, we examined the development of GC in Korean patients with gout. We conducted a nested case-control study using data from 10,174 GC patients and 40,696 control patients from the Korean National Health Insurance Service-National Sample Cohort database. Propensity score matching (1:4) with propensity score overlap-weighted adjustment was used to reduce selection bias and estimate the odds ratio (OR) and 95% confidence intervals (CIs) for the association between gout and GC. An adjusted OR for GC was not significantly higher in patients with gout than in control patients (1.02; 95% CI, 0.93-1.12; p = 0.652). Additionally, no association between gout and GC was observed in subgroup analyses such as sex, age, level of income, region of residence, or Charlson Comorbidity Index score. In conclusion, these results suggest that gout is not a significant independent risk factor for GC among the Korean population. Additional investigation is required to establish a causal association between gout and GC, and to generalize these results to general populations.

Predictors of Early and Late Lung Function Improvement in Severe Eosinophilic Asthma on Type2-Biologics in the PRISM Study.

BACKGROUND: The determinants linked to the short- and long-term improvement in lung function in patients with severe eosinophilic asthma (SEA) on biological treatment (BioT) remain elusive. OBJECTIVE: We sought to identify the predictors of early and late lung function improvement in patients with SEA after BioT. METHODS: 140 adult patients with SEA who received mepolizumab, dupilumab, or reslizumab were followed up for 6 months to evaluate improvement in forced expiratory volume in one second (FEV1). Logistic regression was used to determine the association between potential prognostic factors and improved lung function at 1 and 6 months of treatment. RESULTS: More than a third of patients with SEA using BioT showed early and sustained improvements in FEV1 after 1 month. A significant association was found between low baseline FEV1 and high blood eosinophil count and sustained FEV1 improvement after 1 month (0.54 [0.37-0.79] and 1.88 [1.28-2.97] odds ratios and 95% confidence interval, respectively). Meanwhile, among patients who did not experience FEV1 improvement after 1 month, 39% exhibited improvement at 6 months follow-up. A high ACT score measured at this visit was the most reliable predictor of late response after 6 months of treatment (OR and 95% CI 1.75 [1.09-2.98]). CONCLUSION: Factors predicting the efficacy of biological agents that improve lung function in SEA vary according to the stage of response.

Association between the Use of Proton Pump Inhibitors and Cardiovascular Diseases: A Nested Case-Control Study Using a National Health Screening Cohort.

We investigated the association of proton pump inhibitor (PPI) use with the risk of stroke and ischemic heart disease (IHD). The Korean National Health Insurance Service-Health Screening cohort from 2002 to 2003, the participants of which were followed up until 2019, was used. In study I, 45,905 participants who were diagnosed with stroke were matched with 91,810 control I participants. The history of PPI medication was examined. In study II, 40,928 participants who were diagnosed with IHD were matched with 81,856 control II participants. In both study I and study II, the previous history of PPI medication was examined. A propensity score overlap-weighted multivariable logistic regression analysis was conducted to estimate the overlap-weighted odds ratios (ORs) of PPI use for stroke (study I) and IHD (study II). Current PPI use was linked with higher odds for stroke in study I. The odds for stroke were higher in groups with a longer duration of PPI use (OR = 0.96 [95% CI = 0.92-1.00] < 1.55 [1.50-1.61] < 1.62 [1.57-1.68] for < 30 days, 30 to 180 days, and ≥180 days of PPI use). Previous PPI use was linked with higher odds for IHD in study II. The odds for stroke were higher in groups with a longer duration of PPI use (OR = 1.13 [95% CI = 1.08-1.18] < 2.12 [2.04-2.21] < 2.60 [2.51-2.69] for <30 days, 30 to 180 days, and ≥180 days of PPI use). Current PPI medication is associated with a high risk of stroke and IHD. A longer duration of PPI medication was related to a higher risk of stroke and IHD. However, a prior history of PPI medication was not linked with a high risk of stroke or IHD.

Unlocking the Protective Potential of Upper Respiratory Infection Treatment Histories against Alzheimer's Disease: A Korean Adult Population Study.

With increasing interest in the inflammation-pathogen infection hypothesis and its potential links to Alzheimer's disease (AD) development, there is growing consideration of using upper respiratory infection (URI) treatments as interventions for AD. This nested case-control study explored the potential association between prior URI histories and AD development in a Korean adult population using the national health screening cohort data (2002-2019). The study included 26,920 AD patients and 107,680 matched control individuals, focusing on those seeking respiratory treatment. Logistic regression analyses assessed the impact of URI histories and treatment on AD risk while adjusting for covariates. Our results revealed that over a 1-year period, individuals with URI histories (≥1, ≥2, or ≥3 instances) exhibited decreasing probabilities of developing AD, with risk reductions of 19%, 15%, and 12%, respectively. Expanding our investigation to a 2-year period consistently showed a 17% reduction in AD risk. This effect remained robust across diverse demographic groups and after adjusting for covariates, encompassing comorbidities, hypertension, hyperlipidemia, blood glucose levels, and lifestyle factors. Subgroup analyses further substantiated this association. In conclusion, our findings cautiously suggest a potential protective role of prior URI treatment histories in mitigating the risk of AD development.

Prospective direct comparison of biologic treatments for severe eosinophilic asthma: Findings from the PRISM study.

BACKGROUND: Although various monoclonal antibodies have been used as add-on therapy for severe eosinophilic asthma (SEA), to the best of our knowledge, no direct head-to-head comparative study has evaluated their efficacy. OBJECTIVE: To compare the efficacy of reslizumab, mepolizumab, and dupilumab in patients with SEA. METHODS: This was a multicenter, prospective observational study in patients with SEA who had received 1 of these biologic agents for at least 6 months. Cox proportional hazard models were used to compare the risk of the first exacerbation event, adjusting for sputum or blood eosinophils and common asthma-related covariates. The annual exacerbation rate was analyzed using a negative binomial model, and a mixed-effect model was used to analyze changes in forced expiratory volume in 1 second and asthma control test score over time. RESULTS: A total of 141 patients with SEA were included in the analysis; 71 (50%) received dupilumab; 40 (28%) received reslizumab, and 30 (21%) received mepolizumab. During the 12-month follow-up, 27.5%, 43.3%, and 38.0% of patients in the reslizumab, mepolizumab, and dupilumab groups, respectively, experienced at least 1 exacerbation. However, after adjusting for confounding factors, the dupilumab and mepolizumab groups showed similar outcomes in time-to-first exacerbation, exacerbation rate, forced expiratory volume in 1 second, and asthma control test score to those of the reslizumab group. CONCLUSION: In patients with SEA, treatment with reslizumab, mepolizumab, and dupilumab resulted in comparable clinical outcomes within a 12-month period. TRIAL REGISTRATION: The cohort protocol was sanctioned by the Institutional Review Board of each study center (clinicaltrial.gov identifier NCT05164939).

Gout and Colorectal Cancer Likelihood: Insights from a Nested Case-Control Study of the Korean Population Utilizing the Korean National Health Insurance Service-National Sample Cohort.

Considering the global importance of both gout and colorectal cancer (CRC) as significant health issues with mutual relevance, we aimed to examine the risk of colorectal cancer in Korean patients with gout. In this nested case-control study, we used data from 9920 CRC patients and 39,680 controls the Korean National Health Insurance Service-National Sample Cohort database. Propensity score overlap-weighted multivariate logistic regression analyses, adjusted for confounders, were used to assess the odds ratio (OR) and 95% confidence interval (CI) of the association between gout and CRC. Adjusted OR for CRC were similar between patients with gout and the control group (0.95; 95% CI, 0.86-1.04; p = 0.282). However, after adjustment, subgroup analysis revealed an 18% reduction in the probability of CRC among patients younger than 65 years with gout (95% CI, 0.70-0.95; p = 0.009). Conversely, absence of an association between gout and subsequent CRC persisted regardless of sex, income, residence, and Charlson Comorbidity Index score, even among individuals aged 65 years or older. These results imply that gout may not be a significant independent risk factor for CRC among the general population. However, in patients younger than 65 years with gout, a slightly reduced likelihood of CRC was observed. Further research is necessary to establish a causal relationship between gout and CRC and to generalize these findings to other populations.

Proton Pump Inhibitors and Likelihood of Colorectal Cancer in the Korean Population: Insights from a Nested Case-Control Study Using National Health Insurance Data.

The potential connection between proton pump inhibitors (PPIs) and colorectal cancer (CRC) risk remains unclear, with specific ethnic genetic backgrounds playing a role in PPI-induced adverse effects. In this nested case-control study, we investigated the risk of CRC in relation to preceding PPI use and the duration of use using data from the Korean National Health Insurance Service-National Sample Cohort database, including 9374 incident CRC patients and 37,496 controls. To assess the impact of preceding PPI exposure (past vs. current) and use duration (days: <30, 30-90, and ≥90) on incident CRC, we conducted propensity score overlap-weighted multivariate logistic regression analyses, adjusted for confounding factors. Our findings revealed that past and current PPI users had an increased likelihood of developing CRC. Regardless of duration, individuals who used PPIs also had higher odds of developing CRC. Subgroup analyses revealed that CRC occurrence increased independent of history or duration of prior PPI use, consistent across various factors such as age, sex, income level, and residential area. These findings suggest that PPI use, regardless of past or present use and duration of use, may be related to an increased risk of developing CRC in the Korean population.

A comparison of treatment response to biologics in asthma-COPD overlap and pure asthma: Findings from the PRISM study.

Background: Despite the increasing use of biologics in severe asthma, there is limited research on their use in asthma-chronic obstructive pulmonary disease overlap (ACO). We compared real-world treatment responses to biologics in ACO and asthma. Methods: We conducted a multicenter, retrospective, cohort study using data from the Precision Medicine Intervention in Severe Asthma (PRISM). ACO was defined as post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7 and a smoking history of >10 pack-years. Physicians selected biologics (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) based on each United States Food & Drug Administration (FDA) approval criteria. Results: After six-month treatment with biologics, both patients with ACO (N = 13) and asthma (N = 81) showed positive responses in FEV1 (10.69 ± 17.17 vs. 11.25 ± 12.87 %, P = 0.652), Asthma Control Test score (3.33 ± 5.47 vs. 5.39 ± 5.42, P = 0.290), oral corticosteroid use (-117.50 ± 94.38 vs. -115.06 ± 456.85 mg, P = 0.688), fractional exhaled nitric oxide levels (-18.62 ± 24.68 vs. -14.66 ± 45.35 ppb, P = 0.415), sputum eosinophils (-3.40 ± 10.60 vs. -14.48 ± 24.01 %, P = 0.065), blood eosinophils (-36.47 ± 517.02 vs. -363.22 ± 1294.59, P = 0.013), and exacerbation frequency (-3.07 ± 4.42 vs. -3.19 ± 5.11, P = 0.943). The odds ratio for exacerbation and time-to-first exacerbation showed no significant difference after full adjustments, and subgroup analysis according to biologic type was also showed similar results. Conclusions: Biologics treatment response patterns in patients with ACO and asthma were comparable, suggesting that biologics should be actively considered for ACO patients as well.

Risk for Esophageal Cancer Based on Lifestyle Factors-Smoking, Alcohol Consumption, and Body Mass Index: Insight from a South Korean Population Study in a Low-Incidence Area.

Esophageal cancer constitutes a global public health challenge. However, South Korean population-specific information on the association of lifestyle (smoking, alcohol consumption, and obesity status) with esophageal cancer risk is sparse. This nested case-control study analyzed the Korean national health screening cohort data (2002-2019) of 1114 patients with esophageal cancer and 4456 controls (1:4 propensity-score matched for sex, age, income, and residential region). Conditional and unconditional logistic regression analyses, after adjustment for multiple covariates, determined the effects of lifestyle factors on esophageal cancer risk. Smoking and alcohol consumption increased the esophageal cancer risk (adjusted odds ratio [95% confidence interval]: 1.37 [1.15-1.63] and 1.89 [1.60-2.23], respectively). Overweight (body mass index [BMI] ≥ 23 to <25 kg/m2), obese I (BMI ≥ 25 to <30 kg/m2), or obese II (BMI ≥ 30 kg/m2) categories had reduced odds of esophageal cancer (0.76 [0.62-0.92], 0.59 [0.48-0.72], and 0.47 [0.26-0.85], respectively). In the subgroup analyses, the association of incident esophageal cancer with smoking and alcohol consumption persisted, particularly in men or those aged ≥55 years, whereas higher BMI scores remained consistently associated with a reduced esophageal cancer likelihood across all age groups, in both sexes, and alcohol users or current smokers. Underweight current smokers exhibited a higher propensity for esophageal cancer. In conclusion, smoking and alcohol drinking may potentially increase the risk, whereas weight maintenance, with BMI ≥ 23 kg/m2, may potentially decrease the risk, for esophageal cancer in the South Korean population. Lifestyle modification in the specific subgroups may be a potential strategy for preventing esophageal cancer.

Relationship between heated tobacco product use and allergic rhinitis in Korean adults.

INTRODUCTION: Combustible cigarette (CC) smoking is a risk factor for chronic obstructive pulmonary disease (COPD) and asthma, and some studies reported that tobacco smoking might affect the development or symptom control of allergic rhinitis, sinusitis, and atopic dermatitis. However, evidence on the health risks of heated tobacco products (HTPs) is lacking. We investigated the prevalence of respiratory and allergic diseases according to tobacco use types in Korean adults. METHODS: We used data from 18230 adults in the Korea National Health and Nutrition Examination Survey. Multiple logistic regression analyses were performed to assess the prevalence of respiratory and allergic diseases according to tobacco use types (current exclusive CC use, current exclusive HTPs use, and dual use of CC and HTPs). RESULTS: The prevalence of exclusive CC users, exclusive HTPs users, dual users of CC and HTPs was 15% (n=2740), 1% (n=182), and 2.4% (n=435), respectively. The prevalence of COPD was higher among past tobacco users (AOR=2.37; 95% CI: 1.02-5.51) versus no tobacco use group. The prevalence of asthma was higher among past tobacco users or exclusive CC users (AOR=1.73; 95% CI: 1.26-2.38, and AOR=1.57; 95% CI: 1.08-2.26) versus non-users of tobacco. The prevalence of allergic rhinitis was higher among past tobacco users versus non-users of tobacco (AOR=1.33; 95% CI: 1.13-1.57), and the prevalence of allergic rhinitis was higher among exclusive HTPs users versus non-users of tobacco or exclusive CC users (AOR=1.60; 95% CI: 1.06-2.42, and AOR=1.74; 95% CI: 1.14-2.66). The adjusted odds of sinusitis and atopic dermatitis were not significantly different between tobacco use types. CONCLUSIONS: Exclusive use of HTPs was associated with allergic rhinitis in Korean adults. Further longitudinal studies are needed to clarify the health risk of HTPs.

Current Issues in the Management of IgG Subclass Deficiencies in Adults With Chronic Respiratory Diseases.

Primary immunodeficiency diseases (PIDs) are uncommon in adults; however, immunoglobulin G subclass deficiency (IGGSCD) is often found in a subset of adult patients with chronic respiratory diseases. As quantitative laboratory tests are used to diagnose IGGSCD, the clinical significance of IGGSCD remains controversial. However, respiratory infection is a common presenting feature of IGGSCD, and respiratory complications are responsible for subsequent morbidities, such as severe asthma, bronchiectasis, chronic obstructive airway diseases, and mortality. This review summarizes the current epidemiological data for PIDs, focusing on IGGSCD in the adult population. In addition, the investigation, treatment, and management strategies are detailed, including distinct issues faced by patients with chronic airway disease and their physicians in the proper diagnosis and treatment of IGGSCD.

Alzheimer's Disease and Different Types of Cancer Likelihood: Unveiling Disparities and Potential Protective Effects in a Korean Cohort Study.

The link between Alzheimer's disease and cancer risk is a concern in public health. However, research has yielded limited and sometimes contrasting results, suggesting the need for more validation. We analyzed a large cohort to examine the long-term association between Alzheimer's disease (AD) and the risk of developing cancer. In total, 24,664 AD patients and 98,656 control participants were selected from the National Health Insurance Cohort database of Korea, spanning from 2002 to 2019. Propensity score matching and overlap-weighted adjustment techniques were used to balance the standardized differences between the AD and control groups. The Cox proportional hazards model was applied to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for various cancers, considering relevant covariates. Results indicated that patients with AD had a significantly lower likelihood of overall malignancy (HR 0.63; 95% CI, 0.59-0.68) and each of the 10 site-specific cancers compared to the control group. Among these, pancreatic cancer (HR, 0.50) exhibited the strongest inverse association, followed by hepatic (HR, 0.60), gastric (HR, 0.63), kidney (HR, 0.63), lung (HR, 0.64), thyroid (HR, 0.65), colorectal (HR, 0.67), gallbladder and biliary duct (HR, 0.73), hematologic malignancy (HR, 0.73), and bladder cancers (HR, 0.76). This protective effect against certain organ-specific cancers persisted over the 16-year follow-up period, except for in kidney cancer and hematologic malignancies. The protective effect against specific cancer types (gastric, colorectal, lung, hepatic, and pancreatic) was more prominent in individuals aged 60 years and older, regardless of their sex. However, there were some variations in the specific types of cancer observed between males and females. In summary, Korean patients with AD had a lower risk of cancer, especially in individuals 60 years and older, during the 16-year follow-up period.

An elevated likelihood of stroke, ischemic heart disease, or heart failure in individuals with gout: a longitudinal follow-up study utilizing the National Health Information database in Korea.

Objective: Accumulating evidence from other countries indicates potential associations between gout and cardiovascular diseases; however, the associations of gout with cardiovascular diseases, particularly stroke, ischemic heart disease, and heart failure, remain ambiguous in the Korean population. We hypothesized that individuals with gout are at a higher likelihood of stroke, ischemic heart disease, or heart failure. This study expands upon previous research by ensuring a comparable baseline between patient and control groups and analyzing 16 years of data derived from an extensive healthcare database. Methods: We selected 22,480 patients with gout and 22,480 control individuals from the Korean National Health Insurance Service-Health Screening Cohort database (2002-2019), and matched them at a 1:1 ratio according to sex, age, income, and residence. A Cox proportional hazard model with weighted overlap was employed to examine the relationship between gout and the risk of stroke, ischemic heart disease, or heart failure after adjustment for several covariates. Results: The incidences of stroke, ischemic heart disease, or heart failure in participants with gout were slightly higher than those in controls (stroke: 9.84 vs. 8.41 per 1000 person-years; ischemic heart disease: 9.77 vs. 7.15 per 1000 person-years; heart failure: 2.47 vs. 1.46 per 1000 person-years). After adjustment, the gout group had an 11% (95% confidence interval [CI] = 1.04-1.19), 28% (95% CI = 1.19-1.37), or 64% (95% CI = 1.41-1.91) higher likelihood of experiencing stroke, ischemic heart disease, or heart failure, respectively, than the control group. Conclusion: The present findings suggest that individuals with gout in the Korean population, particularly those aged ≥ 60 years, were more likely to have stroke, ischemic heart disease, or heart failure.

Association between the Use of Statins and Brain Tumors.

This study aimed to investigate the effects of statin use on the incidence of brain tumors. The Korean National Health Insurance Service-National Sample Cohort from 2005 to 2019 was used. The 1893 patients who were diagnosed with brain tumors were matched with 7572 control patients for demographic variables. The history of dyslipidemia was collected, and their history of prescription of statins before diagnosis of brain tumor was examined. The participants without dyslipidemia were set as a reference population. Then, the odds for brain tumors were analyzed in dyslipidemia patients without statin use, dyslipidemia patients who were prescribed statins for less than 365 days, and dyslipidemia patients who were prescribed statins for 365 days or more. Propensity score overlap weighted multivariable logistic regression analysis was used and adjusted for demographics and comorbidities. Secondary analyses were conducted according to types of statins, malignancy of brain tumors, and histories of demographics or comorbidities. A total of 11.78% of brain tumor patients and 10.95% of control participants had histories of statin use for 365 days or more. Dyslipidemia patients with 365 days or more duration of statin use demonstrated 1.22 times higher odds for brain tumors than normal participants (95% confidence intervals [CI] = 1.06-1.14, p = 0.007). Dyslipidemia patients with less than 365 days of statin use had higher odds of brain tumors than other groups (odds ratio = 1.60, 95% CI = 1.36-1.87, p < 0.001). The higher odds for brain tumors in short-term statin users (<365 days) than in long-term statin users (≥365 days) were consistent in secondary analyses according to types of statins, malignancy of brain tumors, and histories of demographics or comorbidities. Long-term statin use in dyslipidemia patients was related to a lower risk of brain tumors than short-term statin use in patients with dyslipidemia.

Changes in the mean incidence and variance of orthopedic diseases before and during the COVID-19 pandemic in Korea: a retrospective study.

BACKGROUND: During the coronavirus disease (COVID-19) pandemic, the amount of moderate- to high-intensity physical activity significantly decreased. Therefore, the epidemiology of musculoskeletal diseases could possibly have changed. We assessed changes in the incidence of and variance in non-traumatic orthopedic diseases before and after the COVID-19 pandemic in Korea. METHODS: This study included data from the Korea National Health Insurance Service, which covers the entire Korean population (approximately 50 million), from January 2018 to June 2021. Using International Classification of Diseases, Tenth Revision codes, 12 common orthopedic diseases were evaluated, including cervical disc disorders, lumbar disc disorders, forward head posture, myofascial pain syndrome, carpal tunnel syndrome, tennis elbow, frozen shoulder, rheumatoid arthritis, gout, hip fracture, distal radius fracture, and spine fracture diseases. "Pre-COVID-19" was the period until February 2020, and "COVID-19 pandemic period" was the period starting March 2020. Differences in the mean incidence and variance of diseases before and during the COVID-19 pandemic were compared. RESULTS: In most cases, the incidence of orthopedic diseases decreased at the beginning of the pandemic and then increased thereafter. Among the 12 diseases, the incidence of three diseases showed a statistically significant change. The incidence of myofascial pain syndrome (P < 0.001) was lower during the COVID-19 pandemic than during the pre-COVID-19 period. The incidences of frozen shoulder (P < 0.001) and gout (P = 0.043) were higher during the COVID-19 pandemic than during the pre-COVID-19 period. However, no statistical difference in disease variations was observed between the two periods. CONCLUSIONS: The incidence of orthopedic diseases varied during the COVID-19 pandemic among the Korean population. Although the incidence of myofascial pain syndrome was lower, that of frozen shoulder and gout was higher during the COVID-19 pandemic than during the pre-COVID-19 period. No disease variations during the COVID-19 pandemic were found.

Exploring the Link between Chronic Kidney Disease and Parkinson's Disease: Insights from a Longitudinal Study Using a National Health Screening Cohort.

Chronic kidney disease (CKD) and Parkinson's disease (PD) are common illnesses found in the geriatric population. A potential link between CKD and PD emergence has been hypothesized; however, existing conclusions are disputed. In this longitudinal research, we analyzed data acquired from the Korean National Health Insurance Service-Health Screening Cohort. The dataset comprised the health information of 16,559 individuals clinically diagnosed with CKD and 66,236 control subjects of comparable ages, all aged ≥40 years. These subjects participated in health examinations from 2002 to 2019. To assess the correlation between CKD and PD, we employed overlap-weighted Cox proportional hazard regression models. The unadjusted, crude hazard ratio for PD was greater in the CKD group than in the control group (crude hazard ration (HR) 1.20; 95% confidence interval (CI) = 1.04-1.39; p = 0.011). However, the Cox proportional hazard regression analysis, incorporating propensity score overlap weighting, revealed no significant discrepancy after considering confounding variables such as demographic factors, socio-economic status, lifestyle, and concurrent health conditions (adjusted HR (aHR), 1.09; 95% CI = 0.97-1.22; p = 0.147). Subgroup analyses showed a higher probability of PD development among certain CKD individuals, including those who resided in rural areas (aHR, 1.19; 95% CI = 1.03-1.37; p = 0.022), maintained a normal weight (aHR, 1.29; 95% CI = 1.08-1.56; p = 0.006), or had fasting blood glucose levels ≥100 mg/dL (aHR, 1.18; 95% CI = 1.00-1.39; p = 0.046). Therefore, these clinical or environmental factors may influence the incidence of PD in CKD patients. In conclusion, our results suggest that the general CKD population may not exhibit a greater propensity for PD than their non-CKD counterparts. However, this might be contingent upon specific lifestyle and comorbid conditions. Thus, certain lifestyle alterations could be crucial in mitigating the potential manifestation of PD in patients diagnosed with CKD.

A higher probability of subsequent stroke and ischemic heart disease in migraine patients: a longitudinal follow-up study in Korea.

BACKGROUND: Whether migraine is related to the risk of cardiovascular diseases (CVDs) remains unclear. Therefore, we conducted a longitudinal follow-up study to address the association between migraine and the development of CVDs in Korea. METHODS: Using data from the national health screening cohort, we included 45,246 patients diagnosed with migraine between 2002 and 2019 and age-, sex-, income-, and residential region-matched nonmigraine participants at a ratio of 1:4. Participants with previous CVDs were excluded. Cox proportional hazards regression models were used to estimate the hazard ratios of three CVDs, stroke, ischemic heart disease, and heart failure, in patients with migraine after adjusting for potential cardiovascular risk factors. RESULTS: The incidence rate differences of stroke, ischemic heart disease, and heart failure among patients with migraine were 2.61, 1.69, and 0.11, respectively. The probability of developing stroke and ischemic heart disease in patients with migraine was significantly higher than that in controls after controlling for multiple confounders (adjusted hazard ratio [HR] = 1.35, 95% confidence interval [CI] = 1.31-1.39 and adjusted HR = 1.31, 95% CI = 1.26-1.35, respectively). However, when compared with the patients without migraine, patients with migraine did not have an increased HR of developing heart failure (adjusted HR = 1.01, 95% CI = 0.95-1.08). The overall migraine group, as well as groups stratified by migraine subtypes with and without aura, each showed a significantly higher probability of subsequent stroke and ischemic heart disease than the control group. CONCLUSIONS: Our longitudinal follow-up study demonstrated a significant association between the presence of migraine and the development of stroke and ischemic heart disease in Korea, even after adjusting for cardiovascular risk factors.