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(1) Background: Recently, a growing number of studies have provided evidence to suggest a strong correlation between air pollution exposure and attention-deficit/hyperactivity disorder (ADHD). In this study, we assessed the relationship between early-life exposure to particulate matter (PM)10, PM2.5, and ADHD; (2) Methods: The National Health Insurance Research Database (NHIRD) contains the medical records, drug information, inspection data, etc., of the people of Taiwan, and, thus, could serve as an important research resource. Air pollution data were based on daily data from the Environmental Protection Administration Executive Yuan, R.O.C. (Taiwan). These included particulate matter (PM2.5 and PM10). The two databases were merged according to the living area of the insured and the location of the air quality monitoring station; (3) Results: The highest levels of air pollutants, including PM2.5 (adjusted hazard ratio (aHR) = 1.79; 95% confidence interval (CI) = 1.58–2.02) and PM10 (aHR = 1.53; 95% CI = 1.37–1.70), had a significantly higher risk of ADHD; (4) Conclusions: As such, measures for air quality control that meet the WHO air quality guidelines should be strictly and uniformly implemented by Taiwanese government authorities.

Taiwan's National Health Insurance Research Database (NHIRD) exemplifies a population-level data source for generating real-world evidence to support clinical decisions and health care policy-making. Like with all claims databases, there have been some validity concerns of studies using the NHIRD, such as the accuracy of diagnosis codes and issues around unmeasured confounders. Endeavors to validate diagnosed codes or to develop methodologic approaches to address unmeasured confounders have largely increased the reliability of NHIRD studies. Recently, Taiwan's Ministry of Health and Welfare (MOHW) established a Health and Welfare Data Center (HWDC), a data repository site that centralizes the NHIRD and about 70 other health-related databases for data management and analyses. To strengthen the protection of data privacy, investigators are required to conduct on-site analysis at an HWDC through remote connection to MOHW servers. Although the tight regulation of this on-site analysis has led to inconvenience for analysts and has increased time and costs required for research, the HWDC has created opportunities for enriched dimensions of study by linking across the NHIRD and other databases. In the near future, researchers will have greater opportunity to distill knowledge from the NHIRD linked to hospital-based electronic medical records databases containing unstructured patient-level information by using artificial intelligence techniques, including machine learning and natural language processes. We believe that NHIRD with multiple data sources could represent a powerful research engine with enriched dimensions and could serve as a guiding light for real-world evidence-based medicine in Taiwan.

Spinal cord injury (SCI) is a devastating disorder. Alcohol abuse has been recognized as hindering SCI patients from rehabilitation, thus leading to longer length of days and poorer prognosis. This article aimed to investigate the association between spinal cord injury (SCI) and alcohol dependence. Data were derived from the National Health Insurance Research Database (NHIRD). The incidence of alcohol dependence between SCI and non-SCI groups was compared. Other possible risk factors were also analyzed. Patients (N = 5670) with SCI from 2000 to 2009 were initially assessed for eligibility. After propensity score matching, 5639 first-time SCI survivors were included. The Cox proportional hazard regression model was used to assess differences in the incidence of alcohol dependence syndrome. Based on the adjusted hazard ratios (HR), the SCI group had a higher hazard for alcohol dependence syndrome compared to the non-SCI group (adjusted HR: 1.39, 95% CI: 1.03~1.86, p = 0.0305). The injury level did not have an impact on the incidence of alcohol dependence syndrome. A higher incidence of alcohol dependence syndrome was related to male patients, lower insurance levels, higher Deyo’s CCI, and psychiatric OPD times. A lower incidence of alcohol dependence syndrome was related to elder age. The incidence of alcohol dependence increased after the occurrence of SCI and was also related to age, sex, monthly income, comorbidities, and psychiatric problems. The injury level did not affect the incidence of alcohol dependence after SCI.

Danshen (salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine. However, it is definite clinical effort and mechanism on breast cancer is unclear. In our study, we used the real-world database to investigate in vivo protective effort of danshen in the breast cancer patients through using population-based data from the Taiwan National Health Insurance Research Database (NHIRD). In vitro , human breast cancer cells (MCF-7 cells and MDA-MB-231 cells) were used to investigate the effect and the underlying mechanism through XTT assay, flow cytometry, glutathione peroxidase (GPX) activity assay, GSH (reduced glutathione)/GSSG (oxidized glutathione), malondialdehyde (MDA), and western blot analysis. The in vivo effect was investigated through a xenograft nude mouse model. We found that dihydroisotanshinone I (DT), a pure compound present in danshen, can inhibit the growth of breast carcinoma cells, including MCF-7 cells and MDA-MB-231 cells. Moreover, DT induced apoptosis and ferroptosis in these breast cancer cells. DT also repressed the protein expression of GPX4 (Glutathione peroxidase 4). For in vivo study, DT treatment also significantly inhibited the final tumor volume without adverse effects in a xenograft nude mouse model. In conclusion, danshen has protective efforts in breast cancer patients, which could be attributed to DT through inducing apoptosis and ferroptosis of breast cancer cells.

This retrospective cohort study is to investigate the association between herpes simplex virus (HSV) infections and dementia, and the effects of anti-herpetic medications on the risk involved, using Taiwan's National Health Insurance Research Database (NHIRD). We enrolled a total of 33,448 subjects, and identified 8362 with newly diagnosed HSV infections and 25,086 randomly selected sex- and age-matched controls without HSV infections in a ratio of 1:3, selected from January 1, to December 31, 2000. A multivariable Cox proportional hazards regression model was used to evaluate the risk of developing dementia in the HSV cohort. This analysis revealed an adjusted hazard ratio of 2.564 (95% CI: 2.351-2.795, P < 0.001) for the development of dementia in the HSV-infected cohort relative to the non-HSV cohort. Thus, patients with HSV infections may have a 2.56-fold increased risk of developing dementia. A risk reduction of dementia development in patients affected by HSV infections was found upon treatment with anti-herpetic medications (adjusted HR = 0.092 [95% CI 0.079-0.108], P < 0.001). The usage of anti-herpetic medications in the treatment of HSV infections was associated with a decreased risk of dementia. These findings could be a signal to clinicians caring for patients with HSV infections. Further research is, therefore, necessary to explore the underlying mechanism(s) of these associations.

Background Numerous studies have verified that insomnia is associated with suicidal ideation, suicide attempts, and death by suicide. Limited population-based cohort studies have been conducted to examine the association. The present study aimed to analyze whether insomnia increases the risk of suicide attempts and verify the effects of insomnia on suicide risk. Methods This study is a cohort study using 2000–2013 hospitalization data from the National Health Insurance Research Database (NHIRD) to track the rate of suicide attempts among insomnia patients aged 15 years or older. In addition, a 1:2 pairing based on sex, age, and date of hospitalization was conducted to identify the reference cohort (patients without insomnia). Cox proportional hazard model was used to assess the effects of insomnia on suicide risk. Results The total number of hospitalized patients aged 15 years or older was 479,967 between 2000 and 2013 (159,989 patients with insomnia and 319,978 patients without insomnia). After adjusting for confounders, suicide risk in insomnia patients was 3.533-fold that of patients without insomnia (adjusted hazard ratio [HR] = 3.533, 95% confidence interval [CI] = 3.059–4.080, P  < 0.001). Suicide risk in low-income patients was 1.434-fold (adjusted HR = 1.434, 95% CI = 1.184–1.736, P  < 0.001) that of non-low-income patients. Suicide risk in patients with drug dependence and with mental disorders was 1.592-fold (adjusted HR = 1.592, 95% CI = 1.220–2.077, P  < 0.001) and 4.483-fold (adjusted HR = 4.483, 95% CI = 3.934–5.109, P  < 0.001) that of patients without drug dependence and without mental disorders, respectively. In the female population, suicide risk in insomnia patients was 4.186-fold (adjusted HR = 4.186, 95% CI = 3.429–5.111, P  < 0.001) that of patients without insomnia. Among patients aged 25–44 years, suicide risk in insomnia patients was 5.546-fold (adjusted HR = 5.546, 95% CI = 4.236–7.262, P  < 0.001) that of patients without insomnia. Furthermore, the suicide risk of insomnia patients with mental disorders was 18.322-fold that of patients without insomnia and mental disorders ( P  < 0.001). Conclusion Insomnia, low income, drug dependence, and mental disorders are independent risk factors for suicide attempts. Female patients and those aged 25–44 years are at high risk of suicide due to insomnia. Insomnia, mental disorders, and low income exhibit a synergistic effect on suicide attempts. Clinicians should pay attention to mental status and income level of insomnia patients.

Stroke severity is an important outcome predictor for intracerebral hemorrhage (ICH) but is typically unavailable in administrative claims data. We validated a claims-based stroke severity index (SSI) in patients with ICH in Taiwan. Consecutive ICH patients from hospital-based stroke registries were linked with a nationwide claims database. Stroke severity, assessed using the National Institutes of Health Stroke Scale (NIHSS), and functional outcomes, assessed using the modified Rankin Scale (mRS), were obtained from the registries. The SSI was calculated based on billing codes in each patient's claims. We assessed two types of criterion-related validity (concurrent validity and predictive validity) by correlating the SSI with the NIHSS and the mRS. Logistic regression models with or without stroke severity as a continuous covariate were fitted to predict mortality at 3, 6, and 12 months. The concurrent validity of the SSI was established by its significant correlation with the admission NIHSS (r = 0.731; 95% confidence interval [CI], 0.705–0.755), and the predictive validity was verified by its significant correlations with the 3-month (r = 0.696; 95% CI, 0.665–0.724), 6-month (r = 0.685; 95% CI, 0.653–0.715) and 1-year (r = 0.664; 95% CI, 0.622–0.702) mRS. Mortality models with NIHSS had the highest area under the receiver operating characteristic curve, followed by models with SSI and models without any marker of stroke severity. The SSI appears to be a valid proxy for the NIHSS and an effective adjustment for stroke severity in studies of ICH outcome with administrative claims data. •Claims data lack stroke severity, a crucial predictor of outcomes after ICH.•The claims-based stroke severity index correlates well with stroke severity in ICH.•Stroke severity index is valid for risk adjustment in studies using claims data.

BackgroundLimited reports have discussed the risk factors for contralateral inguinal hernia (CIH) repair. We generated a risk factor scoring system to predict CIH within 3 years after unilateral inguinal hernia repair.MethodsWe extracted the admission data of patients aged ≥ 18 years who underwent primary unilateral inguinal hernia repair without any other operation from the National Health Insurance Research Database. Patients were randomly divided into 80% and 20% validation cohorts. Multivariate analysis with a logistic regression model was used to generate the scoring system, which was used in the validation group.ResultsOverall, 170,492 adult men were included, with a median follow-up of 87 months. The scoring system ranged from 0–5 points, composited with age (< 45 years, 0 points; 45–65 years, 2 points; 65–80 years, 3 points; > 80 years, 2 points) and two comorbidities (cirrhosis and prostate disease: 1 point each). The areas under receiver operating characteristic (ROC) curves were 0.606 and 0.551 for the derivation and validation groups, respectively. The rates and adjusted odds ratios (OR) of CIH repair in the derivation group were 3.0% at 0–2 points, 5.5% (1.854, p < 0.001) at 3, 6.7% (2.279, p < 0.001) at 4, and 6.9% (2.348, p < 0.001) at 5, with similar results in the validation group [2.3% at 0–2 points, 3.8% (1.668, p < 0.001) at 3, 5.4% (2.386, p < 0.001) at 4, and 6.8% (3.033, p < 0.001) at 5].ConclusionsThe CIH scoring system effectively predicted CIH repair within three years of primary unilateral inguinal hernia repair. Surgeons could perform laparoscopic surgery with CIH scores > 2 points which enables easier contralateral exploration and repair during the same surgery, without additional incisions, to minimize the need for future surgeries. However, further prospective validation of this scoring system is required.

Bladder cancer is the second most common urological malignancy worldwide, with significant morbidity and mortality. This study investigates the association between chronic indwelling catheter (CIDC) use and bladder cancer risk, particularly in relation to comorbidities and complications. Taiwan's National Health Insurance Research Database between 2007 and 2018 was used in this study. Patients with CIDC were identified based on records of catheterization on more than six occasions and matched with two patients without CIDC by age, gender, and index date. The outcome, bladder cancer, was identified using ICD-O-3: C67. The incidence rate of bladder cancer was calculated as the number of bladder cancer cases divided by the total follow-up years during the study period. Cox hazards model was also used to adjust with potential confounding variables. A total of 72,971 CIDC patients and 145,942 matched controls were analyzed. The incidence rate of bladder cancer in the CIDC group was 213.29 per 100,000 person-years, significantly higher than 40.4 per 100,000 person-years in the control group with incidence rate ratio: 5.23 (95% CI: 4.60-5.94, p<.0001). After adjusting with confoundings, patients with CIDC show a 5.16-fold higher risk of bladder cancer compared to those without (95% CI, 4.35-6.13, p<.0001). Subgroup analysis revealed a stronger association in younger patients and females. CIDC-related complications, such as urinary tract stones and benign prostatic hyperplasia (BPH), further increased bladder cancer risk. Our findings suggest a strong association between CIDC use and increased risk of bladder cancer, especially among younger patients and those with urological complications such as BPH and urinary tract stones. Additionally, comorbidities including chronic kidney disease, hypertension, and chronic obstructive pulmonary disease may contribute to this elevated risk. Therefore, an integrated healthcare strategy, including monitoring of comorbidities and complications, early cancer detection, and regular risk assessment, is critical for physicians to effectively manage bladder cancer risk in this population.

INTRODUCTION We investigated the association between the NOTCH3 rs201118034 variant and the risk of ischemic stroke, hemorrhagic stroke, and dementia within a Taiwanese population. METHODS Data from 114,233 individuals enrolled in the Taiwan Biobank were analyzed, integrating clinical diagnoses from the National Health Insurance Research Database and genetic information. Participants were aged 30–70 years and had no history of cancer. Diagnoses were categorized using the International Classification of Diseases, Ninth and Tenth Revisions (ICD‐9/ICD‐10) codes. RESULTS The rs201118034 AG+AA genotype significantly increased the risk of ischemic stroke (odds ratio [OR]: 1.50, 95% confidence interval [CI]: 1.21–1.85, p < 0.001) and hemorrhagic stroke (OR: 2.21, 95% CI: 1.47–3.32, p < 0.001), with no significant link to dementia (p = 0.326). These results imply the role of the rs201118034 variant in elevating stroke risks while its impact on dementia is negligible. DISCUSSION This study highlights the influence of genetic and cardiovascular factors in cerebrovascular diseases and supports the benefit of single nucleotide polymorphism (SNP) ‐based risk stratification. Targeted prevention strategies may be developed for individuals with this genotype. Highlights The study utilized data from over 114,000 individuals in the Taiwan Biobank, integrating clinical diagnoses and genetic information for robust statistical analysis. The rs201118034 AG+AA genotype in the NOTCH3 gene significantly increased the risk of ischemic stroke and hemorrhagic stroke. This variant shows no significant association with dementia, emphasizing the distinct pathways involved in cerebrovascular diseases and cognitive decline.