The association between antiglaucomatous agents and Alzheimer's disease.

OBJECTIVES: To estimate the risk of Alzheimer's disease (AD) associated with long-term use of topical glaucoma medications among middle-aged and older glaucoma patients, and compare the AD risk among various glaucoma subtypes. METHODS: This nationwide population-based cohort study utilized insurance claims data from Taiwan's National Health Insurance Research Database between 2008 and 2019. Participants were adults aged 45 years or older either with a diagnosis of glaucoma or without. Those with glaucoma must have received single antiglaucomatous medication (including α2-adrenergic agonists, cholinergic agonists, beta-blockers, prostaglandin analogs, and pilocarpine) for over 90 days. Those with pre-existing AD diagnoses prior to the index date were excluded. RESULTS: A total of 202,000 participants were included in the study, with 101,000 in each group (glaucoma and control groups). Glaucoma patients on topical alpha-2 adrenergic agonist monotherapy exhibited a significantly higher AD risk (aHR 1.15, 95% CI = 1.01-1.31) compared to those on beta-blockers. Glaucoma was further categorized into primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), primary angle-closure glaucoma (PACG), and unspecified glaucoma. Irrespective of the type of glaucoma, individuals with glaucoma had a significantly higher risk of AD compared to those without glaucoma (POAG: aHR 1.23, 95% CI = 1.08-1.40; NTG: aHR 1.49, 95% CI = 1.19-1.85; PACG: aHR 1.35, 95% CI = 1.19-1.52; unspecified glaucoma: aHR 1.36, 95% CI = 1.23-1.50). CONCLUSIONS: Topical alpha-2 adrenergic agonists might pose increased AD risk in individuals with glaucoma compared to beta-blockers. Accordingly, their utilization should be undertaken judiciously, especially in middle-aged and older populations. Our findings also indicate glaucoma may increase the risk of AD regardless of glaucoma subtype.

Glucagon-like peptide-1 receptor agonists and risk of sight-threatening retinopathy in Taiwanese population: A propensity based cohort study.

AIMS: To compare the risk of vision-threatening retinopathy between glucagon-like peptide-1 receptor agonists (GLP-1 RA) use and no use in patients with type 2 diabetes. METHODS: Using propensity score matching, we identified 27,506 pairs of GLP-1 RA users and non-users, 3904 pairs of GLP-1 RA and dipeptidyl peptidase-4 inhibitors (DPP-4i) users, 10,985 pairs of GLP-1 RA and sodium-glucose cotransporter-2 inhibitors (SGLT2i) users, 2542 pairs of GLP-1 RA and sulfonylurea, respectively, from Taiwan's National Health Insurance Research Database from January 1, 2009 to December 31, 2018. We used Cox proportional hazards models to compare the risk of vision-threatening retinopathy between GLP-1 RA use and other matched groups. RESULTS: In the matched cohorts, the time-varying exposure analysis showed that GLP-1 RA use was not associated with an increased risk of vision-threatening retinopathy compared to GLP-1 RA non-use (aHR 0.96, 95 % CI 0.89-1.03). New-user and active-comparator analyses showed that GLP-1 RA was associated with a significantly lower risk of vision-threatening retinopathy than DPP-4i (aHR 0.8, 95 % CI 0.66-0.97) but had no significant association with this risk compared to SGLT2i (aHR 1.09, 95 % CI 0.96-1.24) or sulfonylureas (aHR 0.79, 95 % CI 0.49-1.06). CONCLUSIONS: This nationwide cohort study showed that GLP-1 RA use was not associated with an increased risk of vision-threatening retinopathy compared to non- GLP-1 RA use, and GLP-1 RA could significantly lower the risk of vision-threatening retinopathy than DPP-4i.

Increased risks of retinal vascular occlusion in patients with migraine and the protective effects of migraine treatment: a population-based retrospective cohort study.

Associations between migraine and retinal vascular occlusion have been reported, but there is no large-scale and comprehensive study. Therefore, we aimed to determine risks of retinal vascular occlusion in patients with migraine. Using the Taiwan National Health Insurance Research Database from 2009 to 2020, we enrolled 628,760 patients with migraine and 628,760 matched individuals without migraine. Study outcomes were diagnoses of retinal vascular occlusion, including retinal artery occlusion (RAO) and retinal vein occlusion (RVO). Adjusted hazard ratio (aHR) of retinal vascular occlusion related to migraine was estimated. The cumulative incidences of subsequent retinal vascular occlusion, RAO, and RVO were significantly higher in migraine patients compared with controls (0.31% vs. 0.21%; 0.09% vs. 0.05%; 0.22% vs. 0.17%; all p < 0.001). The hazards of retinal vascular occlusion, RAO, and RVO were significantly greater in the migraine group (aHR, 1.69 [95% CI, 1.57, 1.83], 2.13 [95% CI, 1.84, 2.48] and 1.53 [95% CI, 1.40, 1.68], respectively). Risks of retinal vascular occlusion were significantly higher in migraine both with aura (MA) and without aura (MO) (aHR, 1.77 [95% CI, 1.58, 1.98], and 1.92 [95% CI, 1.64, 2.25]). Among patients with migraine, nonsteroidal anti-inflammatory drugs, propranolol, and flunarizine significantly reduce their risks of retinal vascular occlusion (aHR, 0.19 [95% CI, 0.16, 0.22], 0.73 [95% CI, 0.62, 0.86], 0.84 [95% CI, 0.76, 0.93]). Migraine, MA and MO are independently associated with higher risks of retinal vascular occlusion, RAO, and RVO.

The risk of herpes zoster is positively associated with obesity, especially morbid obesity.

This study aimed to investigate the association between obesity and herpes zoster (HZ) occurrence. This study used data covering 2 million people in Taiwan in 2000, which were obtained from the National Health Insurance Research Database. The cohort study observed aged 20-100 years with obesity from 2000 to 2017 (tracking to 2018). Obesity was indicated by the presence of two or more outpatient diagnoses or at least one admission record. And, obesity was categorized into non-morbid obesity and morbid obesity. Patients with HZ before the index date were excluded. The obesity cohort and control cohort were matched 1:1 according to age, sex, comorbidities, and index year. There were 18,855 patients in both the obesity and control cohorts. The obesity cohort [adjusted hazard ratio (aHR) 1.09] had a higher risk of HZ than the control cohort. Further analysis, the morbid obesity group (aHR 1.47), had a significantly higher risk of HZ than the non-morbid obesity group. Among the patients without any comorbidities, the patients with obesity had a significantly higher risk of developing HZ than the patients without obesity (aHR 1.18). Obese patients are at a higher risk of HZ development, especially in the patients with morbid obesity. Weight reduction is critical for preventing the onset of chronic diseases and decreasing the risk of HZ in patients with obesity.

The Incidence, Mortality and Medical Expenditure in Patients with Asthma in Taiwan: Ten-year Nationwide Study.

BACKGROUND: This study examines incidence, mortality, medical expenditure and prescription patterns for asthma on a national scale, particularly in Asian countries for asthma is limited. Our aim is to investigate incidence, mortality, prescription patterns and provide a comprehensive overview of healthcare utilization trends for asthma from 2009 to 2018. METHODS: We included patients diagnosed with asthma between 2009 and 2018. We excluded patients with missing demographic data. Our analysis covered comorbidities, including diabetes mellitus, hypertension, allergic rhinitis, eczema, atopic dermatitis, coronary artery disease, congestive heart failure, chronic kidney disease, chronic hepatitis, stroke, and cancer. Investigated medications comprised oral and intravenous steroids, short-acting beta-agonists, inhaled corticosteroids (ICS), combinations of ICS and long-acting beta-agonists, long-acting muscarinic antagonists, and leukotriene receptor antagonists montelukast. We also assessed the number of outpatient visits, emergency visits, and hospitalizations per year, as well as the average length of hospitalization and average medical costs. RESULTS: The study included a final count of 88,244 subjects from 1,998,311 randomly selected samples between 2000 and 2019. Over the past decade, there was a gradual decline in newly diagnosed asthma patients per year, from 10,140 to 6,487. The mean age annually increased from 47.59 in 2009 to 53.41 in 2018. Over 55% of the patients were female. Eczema was diagnosed in over 55% of the patients. Around 90% of the patients used oral steroids, with a peak of 97.29% in 2018, while the usage of ICS varied between 86.20% and 91.75%. Intravenous steroids use rose from 40.94% in 2009 to 54.14% in 2018. The average annual hospital stay ranged from 9 to 12 days, with a maximum of 12.26 days in 2013. Lastly, the average medical expenses per year ranged from New Taiwan dollars 5558 to 7921. CONCLUSIONS: In summary, both asthma incidence and all-cause mortality rates decreased in Taiwan from 2009 to 2018. Further analysis of medical expenses in patients with asthma who required multiple hospitalizations annually revealed an increase in outpatient and emergency visits and hospitalizations, along with longer hospital stays and higher medical costs.

Advancing breastfeeding promotion: leveraging integrative natural galactagogues and unveiling their potential roles-Insights from a 19-year Taiwan nationwide registry to address lactation insufficiency in postpartum women.

Background: Lactation insufficiency is a prevalent challenge for nursing mothers globally. There is a growing interest in the use of herbal galactagogues for enhancing lactation, but their therapeutic efficacy and underlying mechanisms need thorough investigation. This study aims to investigate the efficacy and mechanisms of action of herbal galactagogues in addressing lactation insufficiency by utilizing real-world data and employing a network analysis approach. Methods: Our retrospective study used Taiwan's Longitudinal Health Insurance Database 2000 (LHID2000) to identify 490 patients diagnosed with lactation insufficiency from 2000 to 2018. We analyzed demographic characteristics, co-existing diseases, and prescription patterns for both users and non-users of Chinese herbal products (CHP). Additionally, we utilized a network analysis approach to explore potential compounds and targets in the most frequently used CHP, the Wang Bu Liu Xing and Lu Lu Tong herb pair (WLHP) combination. Results: Out of 490 patients, 81% were CHP users. There were no significant differences in demographic characteristics between CHP users and non-users, but we observed a notable divergence in the prevalence of co-existing diseases. A detailed examination of CHP prescriptions revealed the predominance of WLHP, prompting further investigation. Comprehensive analysis identified 29 major compounds in WLHP, which were associated with 215 unique targets. Intersection analysis revealed 101 overlapping targets between WLHP and lactation, suggesting their potential as therapeutic targets for lactation insufficiency treatment. Topological analysis of the protein-protein interaction (PPI) network identified 13 hub genes potentially crucial for the therapeutic effect of WLHP. Functional enrichment analysis showed that these targets were involved in critical lactation regulation pathways, including the PI3K-Akt signaling pathway, prolactin signaling pathway, estrogen signaling pathway, and AMPK signaling pathway. Discussion: This study emphasizes the potential of CHP, specifically the WLHP combination, in managing lactation insufficiency. The multi-compound, multi-target approach of WLHP and its interaction with key biological processes and signaling pathways offer valuable insights into the underlying mechanisms of its therapeutic effects. These findings warrant further experimental validation and can guide future research and clinical applications of CHP in lactation insufficiency treatment.

Obstructive sleep apnea increases the risk of herpes zoster and postherpetic neuralgia.

OBJECTIVE: Diseases associated with chronic pain are typically a major source of stress for patients; and have been linked to herpes zoster (HZ) development. Here, we investigated whether obstructive sleep apnea (OSA) is a potential stressor that increases the risk of HZ and postherpetic neuralgia (PHN) in affected individuals. METHODS: The data used in this study were obtained from the National Health Insurance Research Database. The study cohort included patients aged between 20 and 100 years who had OSA during the period from 2000 to 2017 (with tracking completed until 2018). The case group and the control group were matched at a 1:1 ratio on the basis of age, sex, comorbidities, and index year, with patients who had outcomes before the index date being excluded. The outcomes considered in this study were HZ and PHN. The risk of HZ and PHN with and without OSA was calculated, and age, sex, comorbidities, and index year were adjusted for. RESULTS: There were 25,211 patients in each group. Patients with OSA had a significantly higher risk of HZ (adjusted hazard ratio [aHR] = 1.22) than those without did. The patients with OSA had also a significantly higher risk of PHN (aHR = 1.36) than those without did. In term of comorbidities, the patients with OSA without (aHR = 1.28) and with (aHR = 1.17) comorbidities had a significantly higher risk of HZ compared with those without OSA. In addition, the patients with OSA but no other comorbidities (aHR = 1.68) had a significantly higher risk of PHN than those without did. CONCLUSION: OSA increases the risk of not only HZ but also PHN. Therefore, patients with OSA should be aware of the potential effect of the disease on their stress levels, as well as the increased risk of developing HZ and PHN.

Non-alcoholic fatty liver disease associated with greater herpes zoster risk than alcoholic fatty liver disease.

BACKGROUND: Disease-related stress can trigger the occurrence of herpes zoster (HZ). Fatty liver disease (FLD) can have adverse effects on the human body and may induce stress in affected individuals. In this study, we investigated whether FLD is associated with an elevated risk of HZ. METHODS: For this study, we utilized data from the National Health Insurance Research Database, patients with FLD from 2000 to 2017 were observed (follow-up until 2018). Patients were considered to have FLD if they had at least two outpatient visits or at least one admission record with a diagnostic code of FLD. Patients with FLD were matched 1:1 by age, sex, comorbidities, and index year with control patients. Additionally, the FLD was further categorized into non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) groups. Multivariable Cox proportional hazards model was used to calculate the incidence rate and adjusted hazard ratio (aHR) of HZ for FLD and AFLD and for various age groups, sex and comorbidities. Cumulative incidence curve for HZ was plotted through the Kaplan-Meier method, and p-value was calculated using the log-rank test. RESULTS: After 1:1 propensity-score matching, each cohort comprised 62,418 patients. The FLD cohort was further divided into NAFLD and AFLD groups, which respectively comprised 55,709 and 6709 patients. The FLD cohort had a risk of HZ significantly higher than that of the control cohort (aHR = 1.06; p < 0.001). Additionally, the NAFLD group exhibited a significantly higher risk of HZ than did the AFLD group (aHR = 1.22; p < 0.001). Among patients without any comorbidities, those with FLD had a higher risk of HZ than did those without FLD (aHR = 1.14; p < 0.001). CONCLUSION: Patients with FLD are at an increased risk of HZ development. Additionally, NAFLD is associated with a higher risk of HZ than AFLD. Therefore, patients with NAFLD should be informed of their increased risk of HZ.

Strong association of lumbar disk herniation with diabetes mellitus: a 12-year nationwide retrospective cohort study.

Background: Despite reports on the association between diabetes mellitus (DM) and lumbar disk herniation (LDH), large-scale, nationwide studies exploring this relationship are lacking. We aimed to examine the profiles of DM in individuals with LDH and explore the potential mechanisms underlying the development of these disorders. Methods: This retrospective, population-based study was conducted between 2008 and 2019 using data from the National Health Insurance (NHI) research database in Taiwan. The primary outcome was the date of initial LDH diagnosis, death, withdrawal from the NHI program, or end of the study period. Results: In total, 2,662,930 individuals with and 16,922,546 individuals without DM were included in this study; 719,068 matched pairs were established following propensity score matching (1:1 ratio) for sex, age, comorbidities, smoking, alcohol consumption, antihyperglycemic medications, and index year. The adjusted risk for developing LDH was 2.33-fold (95% confidence interval: 2.29-2.37; P<0.001), age-stratified analysis revealed a significantly greater risk of LDH in every age group, and both males and females were approximately twice as likely to develop LDH in the DM compared with non-DM cohort. Individuals with DM and comorbidities had a significantly higher risk of developing LDH than those without, and the serial models yielded consistent results. Treatment with metformin, sulfonylureas, meglitinides, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, or alpha-glucosidase inhibitors was associated with a more than 4-fold increased risk of LDH in the DM cohort. DM was strongly associated with the long-term development of LDH; over the 12-year follow-up period, the cumulative risk of LDH was significantly higher in patients with than without DM (log-rank P<0.001). Conclusion: DM is associated with an increased risk of LDH, and advanced DM may indicate a higher risk of LDH.

The Impact of Chronic Pancreatitis on the Occurrences of Human Cancers: Real-World Data.

Chronic pancreatitis (CP) may induce systemic inflammation, potentially increasing cancer susceptibility. However, the link between CP and extra-pancreatic cancer remains underexplored. Employing Taiwanese National Health Insurance Database data from 2000 to 2017, we compared 5394 CP patients with 21,576 non-CP individuals through propensity score matching. CP patients exhibited a significantly higher cancer risk (adjusted hazard ratio (aHR) of 1.32 for females and 1.68 for males) and cumulative incidence (p < 0.001) compared to non-CP individuals. CP showed notable associations with pancreatic (aHR = 3.51), liver (aHR = 1.62), stomach (aHR = 2.01), and other cancers (aHR = 2.09). In terms of liver cancer, CP was significantly associated with patients without viral hepatitis, regardless of gender (aHR = 2.01 for women; aHR = 1.54 for men). No significant cancer occurrences were observed within the first year following CP diagnosis. Pancreatic or liver cancer developed in approximately half of CP patients within 2-3 years, while gastric cancer in male CP patients predominantly occurred around the fifth year after diagnosis. These findings inform potential cancer-screening plans for CP patients.

Exploring the Relationship between Periodontitis, Anti-Periodontitis Therapy, and Extra-Oral Cancer Risk: Findings from a Nationwide Population-Based Study.

This study aimed to evaluate the systemic impact of periodontitis, previously considered a local disease, on cancer occurrence. We enrolled 683,854 participants, comparing cancer incidence among those with and without periodontitis and assessing the impact of periodontal treatment on cancer risk. Regardless of gender, age, Charlson comorbidity index, or the use of non-steroidal anti-inflammatory drugs, periodontitis patients had a lower overall cancer risk than controls. However, men with periodontitis had a higher risk of prostate cancer (adjusted hazard ratio [aHR] = 1.22; 95% confidence interval [CI] = 1.10-1.35), and both men and women had a higher risk of thyroid cancer (women: aHR = 1.20, 95%CI = 1.04-1.38; men: aHR = 1.51, 95% CI = 1.15-1.99). Patients with periodontitis who received treatment showed a reduced cancer risk (aHR = 0.41; 95% CI = 0.38-0.44) compared to untreated patients. Proper treatment for periodontitis may lower an individual's cancer risk more than if they did not have the disease at all, suggesting that periodontitis is a modifiable risk factor for cancer.

Risk of Herpes Zoster in Patients with Pulmonary Tuberculosis-A Population-Based Cohort Study.

BACKGROUND: Pulmonary tuberculosis (TB), a global health problem, is typically caused by the bacterium Mycobacterium tuberculosis. Herpes zoster (HZ) is caused by the reactivation of the varicella-zoster virus (VZV). The reactivation of VZV can be caused by stress. We investigated whether pulmonary TB increases the risk of HZ development. METHODS: This study used data that sampled a population of 2 million people in 2000 from the National Health Insurance Research Database. This cohort study observed Taiwanese patients aged 20-100 years with pulmonary TB from 2000 to 2017 (tracked to 2018). Pulmonary TB was defined as having two or more outpatient diagnoses or at least one admission record. To address potential bias caused by confounding factors, the control cohort and pulmonary TB cohort were matched 1:1 by age, gender, index year, and comorbidities. Patients with HZ before the index date were excluded. RESULTS: A total of 30,805 patients were in the pulmonary TB and control cohorts. The incidence rate of HZ in pulmonary TB and control cohorts were 12.00 and 9.66 per 1000 person-years, respectively. The risk of HZ in the pulmonary TB cohort (adjusted hazard ratios = 1.23; 95% confidence interval = 1.16-1.30) was significantly higher than that of in control cohort. Among patients without comorbidities, the patients with TB were 1.28-fold more likely to have HZ than those without TB. CONCLUSION: Patients with TB should be well treated to avoid the potential risk of HZ occurrence. Although we identified the association between pulmonary TB and HZ, further studies are needed to confirm the result.