OBJECTIVE:To investigate the association between proton pump inhibitor (PPI) use and the risk of peritonsillar abscess (PTA) and deep neck infection (DNI). METHODS:This nested case-control study utilized data from the Health Screening Cohort of the Korean National Health Insurance Service (2002-2013). A total of 1953 patients with PTA and 5797 patients with DNI were identified and matched with controls at a 1:4 ratio based on age, sex, income, and residential area. PPI exposure was classified according to prescription timing and cumulative duration. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using overlap propensity score weighting while adjusting for potential confounders. RESULTS:Current PPI use was associated with an increased risk of PTA (adjusted OR 2.83, 95% CI 2.17-3.68). For DNI, increased odds were observed among both past PPI users (adjusted OR 1.85, 95% CI 1.55-2.21) and current users (adjusted OR 2.80, 95% CI 2.35-3.34). A duration-dependent association was noted for both PTA and DNI, with progressively higher odds ratios observed with longer cumulative PPI exposure (all p < 0.001). CONCLUSIONS:PPI use was associated with increased odds of developing peritonsillar abscess and deep neck infection, particularly among current users and those with prolonged exposure. These findings suggest the need for careful consideration of long-term PPI prescription in clinical practice. However, given the observational design of this study, these findings should be interpreted as an association rather than a causal relationship. LEVEL OF EVIDENCE:Level III.

BACKGROUND:Chronic ischemia in patients with chronic obstructive pulmonary disease (COPD) can increase the risk of inner ear diseases, such as sudden sensorineural hearing loss (SSNHL), Bell's palsy, and Meniere's disease. However, the impact of COPD on these diseases has not been estimated. This study aimed to estimate the risk of SSNHL, Bell's palsy, and Meniere's disease in patients with COPD. METHODS:A total of 582,406 COPD patients were matched with 2,063,063 control participants. The overlap weighted hazard ratios (HRs) of COPD for SSNHL, Bell's palsy, and Meniere's disease were calculated using a propensity score overlap weighted Cox proportional hazard regression model. Secondary analyses were conducted in subgroups according to demographic factors and comorbidities. RESULTS:Overall, 1.00% (5838/582,406), 0.71% (4133/582,406), and 0.75% (4340/582,406) of the COPD patients had SSNHL, Bell's palsy, and Meniere's disease, respectively. The risks of SSNHL, Bell's palsy, and Meniere's disease were 1.06 (95% confidence intervals [CI] = 1.03 - 1.08), 1.05 (1.02 - 1.08), and 1.13 (1.10 - 1.17) times greater, respectively, in COPD patients than in control participants. The increased risk of three diseases in COPD patients was consistent in most of the subgroups. CONCLUSION:Patients with COPD had greater risks of SSNHL, Bell's palsy, and Meniere's disease than did those without COPD. Meniere's disease showed the highest risk related to the presence of COPD.

To determine whether preoperative noncontrast CT features predict early revision after autologous bone cranioplasty and to develop a simple CT-based risk framework. We retrospectively studied adults undergoing autologous cranioplasty at a single center (2010–2020). Preoperative CT variables and clinical indicators were evaluated as candidate predictors in the regression and machine-learning models. The primary outcome was unplanned revision surgery within 30 days. Associations were tested with multivariable logistic regression. A feature-importance derived from the random forest model was used to assess the relative contributions of risk factors. Among 376 patients (mean age 48.9 years; 71.0

Background/Objectives: Psoriasis is a chronic inflammatory disease that significantly impacts physical and emotional health. Statins, primarily used as lipid-lowering drugs, have also demonstrated anti-inflammatory effects. While some studies suggest that statins may improve psoriasis symptoms, the findings have been inconsistent. This study aims to investigate the association between prior statin use and the onset of psoriasis in a Korean population, focusing on individuals with dyslipidemia to minimize confounding factors. Methods: Using the Korean Health Insurance database (2002-2019), a nationwide nested case-control study was conducted, enrolling 8285 participants with psoriasis and 33,140 controls, matched 1:4 for sex, age, residence, and income through propensity scoring. Results: Adjusted odds ratios revealed significantly lower risks of psoriasis among short-term statin users (OR = 0.70, 95% CI = 0.66-0.74) and long-term users (OR = 0.77, 95% CI = 0.73-0.82) than in nonusers. This trend was consistent for both lipophilic and hydrophilic statins, and across subgroup analyses. Conclusions: These findings suggest that statins may reduce the incidence of psoriasis. However, further research is needed to assess their effects on psoriasis progression and severity.

Background: Although several epidemiological studies have suggested a potential association between infections and Parkinson’s disease (PD), relatively few have specifically examined the relationship between upper respiratory tract infections (URIs) and PD, apart from coronavirus disease 2019 (COVID-19). Objectives: We investigated whether a history of URI was associated with the diagnosis of PD among Korean individuals aged ≥40 years, using data from the Korean National Health Insurance Service–Health Screening Cohort. Methods: A total of 5844 patients newly diagnosed with PD were identified and matched with 23,376 control participants at a 1:4 ratio based on age, sex, income, and geographical region. Conditional logistic regression analyses were performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for PD, adjusting for potential confounders including smoking, alcohol consumption, body mass index, blood pressure, comorbidity scores, blood glucose, and serum cholesterol levels. Results: Overall, no significant association was found between a history of URI and PD when considering a two-year exposure window. However, in the one-year window analysis, individuals with a history of URI had a modestly reduced odds of PD (≥1, ≥2, or ≥3 episodes: (adjusted OR: 0.93, 95% CI: 0.88–0.97, aOR: 0.91, 95% CI: 0.87–0.96 and aOR: 0.92, 95% CI: 0.87–0.98, respectively). Subgroup analyses revealed that the inverse association was more pronounced among women, older adults (≥65 years), and those with higher comorbidity scores. No clear dose–response trend was observed across increasing frequencies of URI diagnoses. Conclusions: Our findings suggest that the apparent protective association between recent URI history and PD is unlikely to be causal and may instead reflect confounding by medication use or reverse causation related to the prodromal phase of PD. These results should therefore be interpreted with caution and regarded as hypothesis-generating. Further prospective studies incorporating detailed prescription data and long-term follow-up are warranted to clarify the role of infections and anti-inflammatory medications in the pathogenesis of PD.

Background: Migraine and chronic periodontitis are prevalent conditions that may share common inflammatory and neurovascular pathways. Growing evidence suggests an association between periodontal inflammation and migraine, yet large-scale population-based studies are limited. Objective: To investigate the association between chronic periodontitis and the occurrence of migraine using a nested case-control design in a nationally representative Korean adult cohort. Methods: This study utilized data from the Korean National Health Insurance Service-Health Screening Cohort (2002-2019). A total of 43,359 individuals diagnosed with migraine (ICD-10: G43) were matched 1:4 by age, sex, income, and residence with 173,436 controls. Chronic periodontitis was identified using ICD-10 code K053. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for demographic, behavioral, and clinical covariates. Results: A significant association was observed between chronic periodontitis and migraine. Individuals with at least one diagnosis of periodontitis within one year prior to migraine onset had increased odds of migraine (adjusted OR = 1.10, 95% CI: 1.08-1.13). Similar associations were observed for two diagnoses within one year (OR = 1.05; 95% CI: 1.01-1.09) and one diagnosis within two years (OR = 1.10; 95% CI: 1.08-1.13). No association was found with three or more diagnoses in one year. Subgroup analyses confirmed consistent associations across migraine subtypes and demographic strata. Conclusions: This study demonstrated a statistically significant association between chronic periodontitis and migraine, suggesting a potential shared inflammatory or neurovascular mechanism. Recognizing periodontal disease as a modifiable factor may offer new insights into migraine prevention and management. Further longitudinal and interventional studies are warranted to establish causality.

Background/Objectives: Proton pump inhibitors (PPIs) are widely used for acid-related gastrointestinal disorders, but their potential association with lung cancer risk and mortality remains underexplored and debated. This study sought to investigate the association between PPI use and lung cancer likelihood and mortality, focusing on the impact of PPI exposure history and duration. Methods: This study utilized data from 6795 lung cancer patients, 27,180 matched controls, and 4257 deceased and 2538 surviving lung cancer patients from the Korean National Health Insurance Service’s Health Screening Cohort (2002–2019). Propensity score overlap weighting and logistic regression models were applied to assess the correlations between PPI usage history and duration with lung cancer risk and mortality, while standardized differences ensured balanced baseline characteristics. Results: Overall, PPI use was modestly associated, with a 19% increased likelihood of lung cancer occurrence (95% confidence intervals (CI): 1.12–1.26). Interestingly, prolonged PPI use (≥30 days) was linked to a 13% reduction in lung cancer incidence (95% CI: 0.80–0.94), particularly in subgroups such as older adults (≥70 years), individuals with gastroesophageal reflux disease (GERD) or hypertension, and those with low alcohol consumption. Conversely, overall PPI usage was linked with a 36% increased mortality likelihood among lung cancer patients (95% CI: 1.20–1.55), with prolonged use further correlating with a 27% higher mortality risk (95% CI: 1.05–1.53), especially in high-risk subgroups, including smokers, underweight individuals, and those with hypercholesterolemia or GERD. Conclusions: These findings may suggest a complex and context-dependent relationship between PPI use and lung cancer outcomes, emphasizing the need for individualized risk assessments and careful prescribing practices.

Background/Objectives: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease, but its relationship with gastric cancer (GC) remains unclear. This study aimed to investigate the association between AD and GC using a nationwide Korean database. Methods: Using the Korean National Health Insurance Service-National Sample Cohort, we conducted a nested case–control study including 10,174 GC patients and 40,696 matched controls (1:4 by age, sex, income, and region). Overlap propensity score weighting was used to control for confounders. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated via logistic regression. Results: AD was significantly associated with an increased risk of GC (adjusted OR = 1.08; 95% CI: 1.01–1.15). Subgroup analyses revealed stronger associations among individuals aged ≥ 65 years (OR = 1.12), men (OR = 1.10), rural residents (OR = 1.14), and those without comorbidities (CCI = 0, OR = 1.15). Higher risks were also observed in participants with non-allergic rhinitis (OR = 1.43) or no asthma (OR = 1.12). Conclusions: AD may be associated with an increased risk of GC in the Korean population. These findings may highlight the importance of considering dermatological conditions in the context of systemic cancer risk.

Background/Objectives: Atopic dermatitis (AD) is a common chronic inflammatory skin disease that may influence cancer risk through immune dysregulation and chronic inflammation. The association between AD and colorectal cancer (CRC) remains unclear, with previous studies reporting conflicting results. Evidence from East Asian populations, where CRC incidence is rapidly rising, is particularly limited. Methods: We conducted a nested case–control study using the Korean National Health Insurance Service–National Sample Cohort (2002–2019). A total of 9920 incident CRC cases were identified and matched 1:4 with 39,680 controls by age, sex, income, and residential region. AD was defined using diagnostic codes and prescription records. Overlap propensity score weighting was applied to minimize confounding, and weighted logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Results: AD was not significantly associated with CRC risk (adjusted OR = 0.97, 95% CI: 0.91–1.04). The null association was consistent across subgroups stratified by age, sex, comorbidity burden, and allergic comorbidities. Sensitivity analyses yielded similar results. Conclusions: In this large, nationwide, population-based study, AD did not exhibit a significant connection with the risk of CRC. This null association remained consistent across multiple subgroups and sensitivity analyses, suggesting that AD may not play a substantial role in colorectal carcinogenesis. However, the observational design and lack of detailed lifestyle information may limit causal interpretation.

Background/Objectives: Parkinson's disease (PD) and benign paroxysmal positional vertigo (BPPV) are both prevalent in the geriatric population. While dizziness is a common non-motor symptom in PD, the relationship between PD and incident BPPV remains unclear. Limited data suggest potential shared mechanisms, including mitochondrial dysfunction and oxidative stress, but large-scale epidemiological evidence is lacking. This investigation focused on assessing the incidence of BPPV in patients with PD compared to matched controls using a nationwide cohort. Methods: Data from the Korean National Health Insurance Service-Health Screening Cohort were used to perform a retrospective cohort analysis. We identified 8232 newly diagnosed PD patients and matched them 1:4 with 32,928 controls based on age, sex, income, and residential region. Stratified Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident BPPV. Subgroup and Kaplan-Meier analyses were also performed. Results: Over 220,151 person-years of follow-up revealed a lower incidence of BPPV in the PD group relative to the control group (4.98 vs. 5.95 per 1000 person-years); the corresponding adjusted HR was 0.77 (95% CI: 0.66-0.90; p = 0.001), indicating a 23% reduced risk. The inverse association remained consistent across most subgroups, including older adults and rural residents. Kaplan-Meier analysis further illustrated a significant decline in the cumulative incidence of BPPV in PD patients (p = 0.007). Conclusions: PD may contribute to a lower incidence of BPPV, which could be explained by reduced mobility, altered vestibular function, or diagnostic challenges. Clinicians should consider BPPV in PD patients presenting with dizziness.

Recent studies have reported chronic rhinosinusitis (CRS) as an independent risk factor for stroke. However, the association with stroke depending on the affected sinuses has not been explored. This study aimed to elucidate the side- and sinus-specific relationship between CRS and ischemic stroke through imaging analyses. We retrospectively reviewed the medical records of patients who were diagnosed with ischemic stroke at a tertiary center. CRS was defined as having a total score of greater than or equal to 4, according to the Lund–Mackay scoring system, through brain magnetic resonance imaging or computed tomography. We investigated the side- and sinus-specific correlation between CRS and ischemic stroke. Subgroup analyses were performed for different age groups. CRS prevalence in patients with ischemic stroke was 18.4%, which was higher than the previously reported prevalence in the general population. Overall, there was no correlation between the directions of the CRS and ischemic stroke (p > 0.05). When each sinus was analyzed, the frontal (Cramer’s V = 0.479, p < 0.001), anterior (Cramer’s V = 0.396, p < 0.001)/posterior (Cramer’s V = 0.300, p = 0.008) ethmoid, and sphenoid (Cramer’s V = 0.383, p = 0.005) sinuses showed a statistically significant correlation with the side of stroke, but the maxillary sinus (Cramer’s V = 0.138, p = 0.208) did not. In subgroup analyses, a significant right-side correlation between the two diseases was observed in the older-age subgroup (≥65 years old, Cramer’s V = 0.142, p = 0.040). Diabetes mellitus (odds ratio = 1.596, 95% confidence interval = 1.204–2.116) was identified as an independent risk factor for having CRS in patients with ischemic stroke. CRS of the frontal, anterior/posterior ethmoid, and sphenoid sinuses has a directional relationship with ischemic stroke. Our results on which sinuses correlate with stroke advocate for the active surveillance of CRS in patients at high risk of ischemic stroke.

Objective: Previous studies have reported controversial results on the association between gout and the risk of cancer. This study aimed to investigate the relationship between gout and the incidence of head and neck cancer (HNC). Methods: The data of participants who underwent health checkups in 2009 were analyzed using the National Health Insurance Database in South Korea. A total of 14,348 HNC patients and 57,392 control participants were analyzed for a prior history of gout. Overlap weighting was applied, and odds ratios (ORs) of gout for HNC patients were analyzed. The overlap-weighted model adjusted for demographic, socioeconomic, and lifestyle factors and comorbidities. HNC sites were classified as oral cavity cancer, oropharyngeal cancer, nasopharyngeal cancer, hypopharyngeal cancer, nasal cavity/sinus cancer, larynx cancer, or salivary gland cancer, and the ORs of gout were estimated for each site. Results: Overall, patients with HNC had 1.12-fold greater odds of having gout (95% confidence intervals [CIs] = 1.04–1.20). According to the site of HNC, oral cavity cancer, oropharynx cancer, and larynx cancer demonstrated high odds of having gout (OR = 1.25, 95% CI = 1.16–1.34 for oral cavity cancer; OR = 1.08, 95% CI = 1.01–1.15 for oropharynx cancer; and OR = 1.12, 95% CI = 1.06–1.20 for larynx cancer). On the other hand, nasal cavity/sinus cancer, nasopharynx cancer, and salivary gland cancer presented low odds of having gout (OR = 0.78, 95% CI = 0.72–0.84 for nasal cavity/sinus cancer; OR = 0.89, 95% CI = 0.83–0.96 for nasopharynx cancer; and OR = 0.88, 95% CI = 0.81–0.96 for salivary gland cancer). Conclusions: A prior history of gout was associated with a high overall incidence of HNC. Oral cavity cancer, oropharynx cancer, and larynx cancer have a high incidence in gout patients. However, nasal cavity/sinus cancer, nasopharyngeal cancer, and salivary gland cancer have low incidences in gout patients. The impact of gout on HNC risk should be specifically considered according to the site of the HNC.

AbstractThis study constructed deep learning models using plain skull radiograph images to predict the accurate postnatal age of infants under 12 months. Utilizing the results of the trained deep learning models, it aimed to evaluate the feasibility of employing major changes visible in skull X-ray images for assessing postnatal cranial development through gradient-weighted class activation mapping. We developed DenseNet-121 and EfficientNet-v2-M convolutional neural network models to analyze 4933 skull X-ray images collected from 1343 infants. Notably, allowing for a ± 1 month error margin, DenseNet-121 reached a maximum corrected accuracy of 79.4% for anteroposterior (AP) views (average: 78.0 ± 1.5%) and 84.2% for lateral views (average: 81.1 ± 2.9%). EfficientNet-v2-M reached a maximum corrected accuracy 79.1% for AP views (average: 77.0 ± 2.3%) and 87.3% for lateral views (average: 85.1 ± 2.5%). Saliency maps identified critical discriminative areas in skull radiographs, including the coronal, sagittal, and metopic sutures in AP skull X-ray images, and the lambdoid suture and cortical bone density in lateral images, marking them as indicators for evaluating cranial development. These findings highlight the precision of deep learning in estimating infant age through non-invasive methods, offering the progress for clinical diagnostics and developmental assessment tools.

Growing research has proposed that rheumatoid arthritis (RA) and chronic periodontitis (CP) share similar pathophysiological mechanisms involving inflammation and tissue destruction. However, the potential correlation of CP as a contributing factor for the occurrence of RA warrants validation in the Korean population, where both diseases are prevalent, especially considering the increasingly aging demographic in Korea. This study examined 5139 RA cases and 509,727 matched controls from a Korean national cohort dataset (2002–2019) by carefully employing propensity score matching to ensure comparability between groups. Baseline characteristics were compared using standardized differences, and logistic regression was employed to estimate the impact of CP history on RA likelihood while controlling for covariates. We fully examined medical records documenting CP occurrences within the two-year period leading up to the index date, conducting comprehensive subgroup analyses. While a 1-year history of CP did not show a significant association with likelihood of RA, a 2-year history of CP increased RA likelihood by 12%, particularly among older adults, females, rural residents, and those with certain comorbidities such as hypercholesterolemia. Interestingly, this association persisted even among individuals with non-smoking habits, normal weight, and infrequent alcohol consumption. These findings suggest that chronic CP exposure for at least 2 years may independently elevate RA risk in Korean adults. The association in certain subgroups appears to suggest a predisposition toward genetic susceptibilities over lifestyle and environmental factors. Predicting RA in CP patients may be challenging, emphasizing the importance of regular RA screening, especially in high-risk subgroups.

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.

Gastric cancer (GC) survivors may be more likely to develop osteoporosis. However, few studies on the relationship between GC and osteoporosis have been conducted on large patient populations. We aimed to determine the incidence of osteoporosis and identify related factors by comparing patients with GC and matched controls using the Korean National Health Insurance Service—National Sample Cohort (KNHIS-NSC). This study included 9078 patients with GC and 36,312 controls (1:4 propensity score-matched for sex, age, residence, and income). The hazard ratio (HR) for osteoporosis was significantly greater for GC patients than for controls according to Charlson Comorbidity Index (CCI) score-adjusted models (adjusted HR = 1.13). Kaplan–Meier analysis revealed that the cumulative incidence of osteoporosis during the follow-up period commencing from the index date was significantly greater in GC patients than in the controls (p = 0.0087). A positive correlation of osteoporosis with GC was detected for those aged < 65 years, males, and those with CCI scores = 0. In conclusion, the study findings suggest that men with GC aged < 65 years may be at an increased risk for osteoporosis. Research into additional risk factors and the optimal timing of interventions are needed to prevent fractures and minimize bone loss in GC survivors.

This study explores the progression of intracerebral hemorrhage (ICH) in patients with mild to moderate traumatic brain injury (TBI). It aims to predict the risk of ICH progression using initial CT scans and identify clinical factors associated with this progression. A retrospective analysis of TBI patients between January 2010 and December 2021 was performed, focusing on initial CT evaluations and demographic, comorbid, and medical history data. ICH was categorized into intraparenchymal hemorrhage (IPH), petechial hemorrhage (PH), and subarachnoid hemorrhage (SAH). Within our study cohort, we identified a 22.2% progression rate of ICH among 650 TBI patients. The Random Forest algorithm identified variables such as petechial hemorrhage (PH) and countercoup injury as significant predictors of ICH progression. The XGBoost algorithm, incorporating key variables identified through SHAP values, demonstrated robust performance, achieving an AUC of 0.9. Additionally, an individual risk assessment diagram, utilizing significant SHAP values, visually represented the impact of each variable on the risk of ICH progression, providing personalized risk profiles. This approach, highlighted by an AUC of 0.913, underscores the model’s precision in predicting ICH progression, marking a significant step towards enhancing TBI patient management through early identification of ICH progression risks.

Despite growing interest in the preventive effects of statins, as lipid-lowering agents, on migraine attacks, comprehensive nationwide studies comparing migraine likelihood between statin users and controls are lacking. Our nested case–control study within the Korean National Health Insurance Service-Health Screening Cohort (2002–2019) investigated this association using 38,957 migraine patients and 155,828 controls, considering migraine subtypes (with/without aura) and statin types (lipophilic vs. hydrophilic). Using propensity score matching and adjusting for confounders, statin use was linked to reduced migraine likelihood overall (odds ratio (OR) 0.93), particularly for migraines with aura (OR 0.75) and without aura (OR 0.94). Lipophilic statins were effective for both subtypes, while hydrophilic statins mainly reduced the likelihood of migraines without aura. Subgroup analyses showed consistent benefits across demographics, but varied effectiveness based on weight, smoking, alcohol use, hemoglobin levels, and dyslipidemia history. In summary, this nationwide cohort study suggests that statin use may reduce migraine likelihood among Korean adults across diverse demographics and clinical profiles, but varied effectiveness based on certain lifestyle and comorbidity factors underscores the importance of considering individual patient profiles when assessing the potential benefits of statin therapy for migraine prevention.

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.

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.