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Abstract We appreciate your interest in our study. This study contrasts with Dorney et al.‘s focus on the first 21 days. We conducted a re-analysis regarding selection bias and found consistent results. Our research highlights the elevated risk of retinal vascular occlusion after vaccination, which can last up to two years. We also discussed the differences in study design and the effects of different vaccine brands.

Background: Many patients who recovered from COVID-19 still suffer from chronic fatigue syndrome (CFS). It was observed that patients with comorbidities were more prone to developing CFS. This research investigates the risk of post-COVID-19 CFS to assist healthcare professionals in reducing the risk of CFS. Methods: A retrospective cohort study is conducted to investigate the risk of post-COVID-19 CFS based on the TriNetX-sourced electronic health records. Factors including age, sex, race, vaccination, and severity of COVID-19 are analysed. Propensity score matching was applied to balance COVID-19 and non-COVID-19 cohorts. Kaplan-Meier analysis and Cox proportional hazard model were used to perform the relationship between COVID-19 and CFS risk. Results: This research involved 3227281 patients with COVID-19 and 3227281 with non-COVID-19 between 1st January 2020 and 31st December 2023. The incidence of CFS was higher in the COVID-19 group compared to the non-COVID-19 group at 1 follow-up intervals (HR 1.59, 95 % CI = 1.54–1.63). Subgroup analysis revealed increased CFS risk across different age groups (>18), sexes, races, and comorbid conditions, with notable variations. Conclusions: COVID-19 patients have a higher risk of developing CFS compared to individuals without COVID-19. The increased risk is particularly significant in adults aged 18 years and older.

Summary: Background: Autoimmune diseases are known to be associated with an increased risk of cancer. Whether maternal immune dysregulation can have an impact on the development of haematological malignancies in offspring remains uncertain. Therefore, we explored the association between offspring risk of haematological malignancies and maternal autoimmune disease using a real-world nationwide population-based study. Methods: In this case–control study, we identified 2172 children with haematological malignancies between 2004 and 2019 from Taiwan's National Health Insurance program and compared them with population-based controls without haematologic malignancies, who were matched with each individual at a ratio of 1:4. The medical information of the autoimmune mothers were obtained from the Taiwan Maternal and Child Health Database. Conditional logistic regression was used to estimate the odds ratio for haematologic malignancy in offspring. Furthermore, subgroup and stratified analyses were conducted. Findings: Among the rheumatologic diseases in our study, Crohn's disease was the most common disease both in the haematological malignancy group (1.1%) and the control group (0.9%). In multivariable analysis, the odds ratio for haematological malignancy in offspring with maternal autoimmune diseases was 1.2 (95% confidence interval [CI] 0.91–1.58). The overall risk of haematologic malignancy was not significantly higher when adjusted for specific risk factors, including neonatal age, maternal age, family income, urbanization, maternal occupation, birth weight, or maternal comorbidity, except for prematurity. When comparing different autoimmune diseases among haematological malignancies and the control group, maternal psoriatic arthritis/psoriasis had the highest adjusted overall risk for haematological malignancies (adjusted OR 2.11, CI 0.89–5), followed by ankylosing spondylitis (adjusted OR 1.45, CI 0.7–3), autoimmune thyroiditis (OR 1.26, CI 0.57–2.81), systemic lupus erythematosus (OR 1.21, CI 0.48–3.02), Crohn's disease (OR 1.19, CI 0.75–1.9), and Sjogren's syndrome (OR 1.18, CI 0.65–2.15), but no significance was reached in these analyses. Multivariable analysis of risk factors associated with haematological malignancy subtypes was done. It showed no associations between maternal autoimmune disease and childhood haematological malignancies. Interpretation: We found no significant relationship between maternal autoimmune disease and childhood haematological malignancies. The influence of maternal immune dysregulation on the next generation with respect to haematological malignancies development may be limited. Funding: There was no funding source for this study.

Abstract Background Paxlovid has been shown to be effective in reducing mortality and hospitalization rates in patients with coronavirus disease 2019 (COVID-19). It is not known whether Paxlovid can reduce the risk of cardiovascular diseases (CVD) in COVID-19-surviving patients with autoimmune rheumatic diseases (AIRDs). Methods TriNetX data from the US Collaborative Network were used in this study. A total of 5,671,395 patients with AIRDs were enrolled between January 1, 2010, and December 31, 2021. People diagnosed with COVID-19 were included in the cohort (n = 238,142) from January 1, 2022, to December 31, 2022. The Study population was divided into two groups based on Paxlovid use. Propensity score matching was used to generate groups with matched baseline characteristics. The hazard ratios (HRs) and 95% confidence intervals of cardiovascular outcomes, admission rate, mortality rate, and intensive care unit (ICU) admission rate were calculated between Paxlovid and non-Paxlovid groups. Subgroup analyses on sex, age, race, autoimmune diseases group, and sensitivity analyses for Paxlovid use within the first day or within 2–5 days of COVID-19 diagnosis were performed. Results Paxlovid use was associated with lower risks of cerebrovascular complications (HR = 0.65 [0.47–0.88]), arrhythmia outcomes (HR = 0.81 [0.68–0.94]), ischemic heart disease, other cardiac disorders (HR = 0.51 [0.35–0.74]) naming heart failure (HR = 0.41 [0.26–0.63]) and deep vein thrombosis (HR = 0.46 [0.24–0.87]) belonging to thrombotic disorders in AIRD patients with COVID-19. Compared with the Non-Paxlovid group, risks of major adverse cardiac events (HR = 0.56 [0.44–0.70]) and any cardiovascular outcome mentioned above (HR = 0.76 [0.66–0.86]) were lower in the Paxlovid group. Moreover, the mortality (HR = 0.21 [0.11–0.40]), admission (HR = 0.68 [0.60–0.76]), and ICU admission rates (HR = 0.52 [0.33–0.80]) were significantly lower in the Paxlovid group than in the non-Paxlovid group. Paxlovid appears to be more effective in male, older, and Black patients with AIRD. The risks of cardiovascular outcomes and severe conditions were reduced significantly with Paxlovid prescribed within the first day of COVID-19 diagnosis. Conclusions Paxlovid use is associated with a lower risk of CVDs and severe conditions in COVID-19-surviving patients with AIRD.

Background The Assessment of SpondyloArthritis international Society-European Alliance of Associations for Rheumatology recommendations for axial spondyloarthritis (axSpA) management include patient assessment for biological disease-modifying antirheumatic drug (bDMARD) treatment response after at least 12 weeks of treatment. The current treat-to-target strategy for axSpA is to achieve inactive disease (ID; Axial Spondyloarthritis Disease Activity Score (ASDAS)

IntroductionTo verify our hypothesis that psoriatic arthritis (PsA) is mainly genetically predetermined and distinct from psoriasis (PsO), we use the TriNetX database to investigate whether intrinsic factors outweigh externals in PsA emergence in PsO patients.MethodsWe conducted three retrospective cohort studies utilizing information from the TriNetX network, whether (a) PsO patients with type 2 diabetes mellitus (DM) face an elevated risk of developing PsA compared to those without type 2 DM; (b) PsO patients who smoke face a higher risk of PsA; and (c) PsO patients with type 2 DM who smoke are more likely to develop PsA than those who do not smoke.ResultsPsO patients with type 2 DM exhibited an elevated risk of developing PsA [hazard ratio (HR), 1.11; 95% CI 1.03–1.20], with the combined outcome demonstrating a heightened HR of 1.31 (95% CI 1.25–1.37). PsO patients with a smoking history exhibited an elevated risk of developing PsA (HR, 1.11; 95% CI 1.06–1.17), with the combined outcome demonstrating a heightened HR of 1.28 (95% CI 1.24–1.33). PsO patients with type 2 DM and a history of smoking were not found to be associated with an increased risk of developing PsA (HR, 1.05; 95% CI 0.92–1.20). However, the combined result revealed a higher risk of 1.15 (95% CI 1.06).DiscussionThese findings suggested that intrinsic factors outweigh external factors in PsA emergence in PsO patients. Further studies may focus on genetic disparities between PsO and PsA as potential risk indicators rather than solely on phenotypic distinctions.

Context: Recently, new intervention tools at the mild cognitive impairment (MCI) stage are needed to prevent dementia, including Alzheimer’s disease (AD). Aims: To evaluate whether a standardized Asparagus officinalis stem (ETAS) extract, as a functional ingredient, effectively maintains cognitive functions in subjects with normal aging and MCI. Methods: A pilot randomized controlled trial was conducted on thirty subjects that were randomly allocated to the experimental group (n = 15), which received ETAS supplementation (1,000 mg) daily, and a control group, which received placebo (dextrin) in the same form (n = 15) for a period of 12 months. All subjects were evaluated using neuropsychological questionnaires comprised of Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), Clock Drawing Test (CDT), and Hospital Anxiety and Depression Scale (HADS) at all visit times. Brain tests (MRI, EEG and EPB) and blood tests (hematology, hemochemistry, immunological status and HSP70) were also performed. Primary endpoints were the change in the neuropsychological questionnaire scores. Secondary endpoints such as immunological and molecular biomarkers of dementia, neurological imaging, and electrophysiological outcomes were measured. Results: The ETAS group showed a significant improvement in scores on MMSE, FAB, and HADS, tended to improve in scores on CDT, and could show a slight increase in blood HSP70. The ETAS group also maintained normal levels of CD4/CD8 immune complex. No adverse events were detected during the study period. Conclusions: ETAS supplementation could prevent the progression of cognitive decline and anxiety/depression expression associated with the prevention of AD.

Abstract Background Patients with type 2 diabetes (T2D) tend to have nonalcoholic fatty liver disease (NAFLD) with poorer prognosis. We performed this research to compare the risks of cardiovascular diseases, cirrhosis, liver-related mortality, and cardiovascular mortality between glucagon-like peptide-1 receptor agonist (GLP-1 RA) use and no-use in patients with T2D without viral hepatitis. Methods From January 1, 2008, to December 31, 2018, we used propensity-score matching to identify 31,183 pairs of GLP-1 RA users and nonusers from Taiwan’s National Health Insurance Research Database. Multivariable-adjusted Cox proportional hazards models were used to examine the outcomes between the study and control groups. Results The median (Q1, Q3) follow-up time for GLP-1 RA users and nonusers were 2.19 (1.35, 3.52) and 2.14 (1.19, 3.68) years, respectively. The all-cause mortality incidence rate was 5.67 and 13.06 per 1000 person-years for GLP-1 RA users and nonusers, respectively. Multivariable-adjusted analysis showed that GLP-1 RA use had significantly lower risks of all-cause mortality (aHR 0.48, 95%CI 0.43–0.53), cardiovascular events (aHR 0.92, 95%CI 0.86–0.99), cardiovascular death (aHR 0.57, 95%CI 0.45–0.72), and liver-related death (aHR 0.32, 95%CI 0.13–0.75). However, there was no significant difference in the risk of liver cirrhosis development, hepatic failure, and hepatocellular carcinoma compared to GLP-1 RA no-use. Conclusions This nationwide cohort study showed that GLP-1 RA use was associated with a significantly lower risk of all-cause mortality, cardiovascular events, and cardiovascular death in patients with T2D among Taiwan population. More prospective studies are warranted to verify our results.

ObjectiveTo compare the effects of tofacitinib and adalimumab on the risk of adverse lipidaemia outcomes in patients with newly diagnosed rheumatoid arthritis (RA).MethodsData of adult patients newly diagnosed with RA who were treated with tofacitinib or adalimumab at least twice during a 3-year period from 1 January 2018 to 31 December 2020, were enrolled in the TriNetX US Collaborative Network. Patient demographics, comorbidities, medications, and laboratory data were matched by propensity score at baseline. Outcome measurements include incidental risk of dyslipidemia, major adverse cardiac events (MACE) and all-cause mortality.ResultsA total of 7,580 newly diagnosed patients with RA (1998 receiving tofacitinib, 5,582 receiving adalimumab) were screened. After propensity score matching, the risk of dyslipidaemia outcomes were higher in the tofacitinib cohort, compared with adalimumab cohort (hazard ratio [HR] with 95% confidence interval [CI], 1.250 [1.076–1.453]). However, there is no statistically significant differences between two cohorts on MACE (HR, 0.995 [0.760–1.303]) and all-cause mortality (HR, 1.402 [0.887–2.215]).ConclusionTofacitinib use in patients with RA may increase the risk of dyslipidaemia to some extent compared to adalimumab. However, there is no differences on MACE and all-cause mortality.

Abstract The relationship between Helicobacter pylori infection and rheumatoid arthritis has been investigated, but the results remain controversial. This study aims to determine the association between the two diseases via a 17-year retrospective cohort study. Using the National Health Insurance Research Database, a nationwide population based in Taiwan, we identified 97,533 individuals with H. pylori infection and matched controls between 2000 and 2017 using propensity score matching at a 1:1 ratio. The adjusted hazard ratio of rheumatoid arthritis was determined by multiple Cox regression. The incidence rate of rheumatoid arthritis was 1.28 per 10,000 person-months in the H. pylori cohort, with a higher risk compared to the control group. In the

There is a knowledge gap concerning the proper timing for COVID-19 vaccination in cancer patients undergoing chemotherapy. We aimed to evaluate the suitability of the guidelines that recommend waiting at least three months after undergoing chemotherapy before receiving a COVID-19 vaccine. This retrospective cohort study used aggregated data from the TriNetX US Collaboratory network. Participants were grouped into two groups based on the interval between chemotherapy and vaccination. The primary outcome assessed was infection risks, including COVID-19; skin, intra-abdominal, and urinary tract infections; pneumonia; and sepsis. Secondary measures included healthcare utilization and all causes of mortality. Kaplan–Meier analysis and the Cox proportional hazard model were used to calculate the cumulative incidence and hazard ratio (HR) and 95% confidence intervals for the outcomes. The proportional hazard assumption was tested with the generalized Schoenfeld approach. Four subgroup analyses (cancer type, vaccine brand, sex, age) were conducted. Sensitivity analyses were performed to account for competing risks and explore three distinct time intervals. Patients receiving a vaccine within three months after chemotherapy had a higher risk of COVID-19 infection (HR: 1.428, 95% CI: 1.035–1.970), urinary tract infection (HR: 1.477, 95% CI: 1.083–2.014), and sepsis (HR: 1.854, 95% CI: 1.091–3.152) compared to those who adhered to the recommendations. Hospital inpatient service utilization risk was also significantly elevated for the within three months group (HR: 1.692, 95% CI: 1.354–2.115). Adhering to a three-month post-chemotherapy waiting period reduces infection and healthcare utilization risks for cancer patients receiving a COVID-19 vaccine.

The communication gap between patients and health care professionals has led to increased disputes and resource waste in the medical domain. The development of artificial intelligence and other technologies brings new possibilities to solve this problem. This viewpoint paper proposes a new relationship between patients and health care professionals—“shared decision-making”—allowing both sides to obtain a deeper understanding of the disease and reach a consensus during diagnosis and treatment. Then, this paper discusses the important impact of ChatGPT-like solutions in treating rheumatoid arthritis using methotrexate from clinical and patient perspectives. For clinical professionals, ChatGPT-like solutions could provide support in disease diagnosis, treatment, and clinical trials, but attention should be paid to privacy, confidentiality, and regulatory norms. For patients, ChatGPT-like solutions allow easy access to massive amounts of information; however, the information should be carefully managed to ensure safe and effective care. To ensure the effective application of ChatGPT-like solutions in improving the relationship between patients and health care professionals, it is essential to establish a comprehensive database and provide legal, ethical, and other support. Above all, ChatGPT-like solutions could benefit patients and health care professionals if they ensure evidence-based solutions and data protection and collaborate with regulatory authorities and regulatory evolution.

ObjectiveTo explore the associations between the use of immune checkpoint inhibitors (ICIs) and the risk of developing uveitis among cancer patients.MethodsCancer patients who received ICI therapy and a comparison group of cancer patients who did not receive ICI therapy were retrospectively recruited from the TriNetX electronic heath-record registry. The outcome of interest was the development of new-onset uveitis. Propensity score matching based on a 1:1 ratio was conducted in order to reduce bias. Multi-variate cox proportional hazard models and Kaplan Meier method were also utilized to assess for the risk of uveitis among cancer patients who received ICI therapy.Results71931 cancer patients (54.7% male; 76.5% white; mean age at index 63.6 ± 12.2 years) who received ICI treatment (ICI group) and 71931 cancer patients (54.7% male; 77% white; mean age at index 63.5 ± 12.4 years) who never received ICI (comparison group) were recruited. Associated Kaplan-Meier curves showed significantly increased uveitis risk among the ICI group for all follow-up years (p

Kawasaki disease (KD) is an inflammatory vasculitis disorder of unknown etiology. It is a rare but fatal disease and the leading cause of acquired coronary heart disease in children under the age of 5 years. We examined the association of KD with the demographics of family members, parents' characteristics, and perinatal factors in Taiwanese children. This nested case-control study used data from Taiwan's Health and Welfare Data Science Center and initially included children born in Taiwan between January 1, 2006, and December 31, 2015 (n = 1,939,449); the children were observed for KD development before the age of 5 years (n = 7870). The control group consisted of children without KD who were matched with each KD case by sex and birth date at a ratio of 8:1. The odds ratio (ORs) of the aforementioned associations were estimated using conditional logistic regression. The risk of KD decreased in children with younger parents [

Abstract Background This study compared the risks of cardiovascular morbidity and mortality between patients with type 2 diabetes (T2D) with and without microvascular diseases, and between matched patients with microvascular diseases. Methods We identified newly diagnosed type 2 diabetes patients from National Health Insurance Research Database in Taiwan from January 1, 2008, to December 31, 2019. Propensity score matching was applied to construct matched pairs of patients with diabetic kidney disease, retinopathy, or neuropathy. Multivariable Cox proportional-hazard models were adopted to compare the risks of cardiovascular morbidity and mortality. Results Patients with microvascular disease had a significantly higher risk of cardiovascular morbidities and mortality than those without microvascular disease. Among the matched cohorts, patients with diabetic retinopathy had a significantly higher risk of stroke development than those with diabetic kidney disease (aHR 1.11, 95%CI 1.03–1.2). Diabetic neuropathy showed a significantly higher risk of stroke development than diabetic kidney disease (aHR 1.17, 95%CI 1.1–1.25) and diabetic retinopathy (aHR 1.12, 95%CI 1.03–1.21). Diabetic retinopathy had a significantly higher risk of incident heart failure than diabetic kidney disease (aHR 1.43, 95%CI 1.3–1.57), and diabetic neuropathy had a significantly lower risk of incident heart failure than diabetic retinopathy (aHR 0.79, 95%CI 0.71–0.87). Conclusions T2D patients with microvascular disease have a significantly higher risk of cardiovascular morbidities and mortality than those without microvascular disease. In the matched cohorts, diabetic neuropathy was significantly associated with stroke development, and diabetic retinopathy had a significant association with heart failure compared to other microvascular diseases.

Abstract Coronavirus disease 2019 (COVID-19) vaccines are associated with several ocular manifestations. Emerging evidence has been reported; however, the causality between the two is debatable. We aimed to investigate the risk of retinal vascular occlusion after COVID-19 vaccination. This retrospective cohort study used the TriNetX global network and included individuals vaccinated with COVID-19 vaccines between January 2020 and December 2022. We excluded individuals with a history of retinal vascular occlusion or those who used any systemic medication that could potentially affect blood coagulation prior to vaccination. To compare the risk of retinal vascular occlusion, we employed multivariable-adjusted Cox proportional hazards models after performing a 1:1 propensity score matching between the vaccinated and unvaccinated cohorts. Individuals with COVID-19 vaccination had a higher risk of all forms of retinal vascular occlusion in 2 years after vaccination, with an overall hazard ratio of 2.19 (95% confidence interval 2.00–2.39). The cumulative incidence of retinal vascular occlusion was significantly higher in the vaccinated cohort compared to the unvaccinated cohort, 2 years and 12 weeks after vaccination. The risk of retinal vascular occlusion significantly increased during the first 2 weeks after vaccination and persisted for 12 weeks. Additionally, individuals with first and second dose of BNT162b2 and mRNA-1273 had significantly increased risk of retinal vascular occlusion 2 years following vaccination, while no disparity was detected between brand and dose of vaccines. This large multicenter study strengthens the findings of previous cases. Retinal vascular occlusion may not be a coincidental finding after COVID-19 vaccination.

Abstract To study whether hydroxychloroquine (HCQ) therapy increases the risks of cataracts in patients with rheumatoid arthritis (RA). In this retrospective cohort study, 2821 treatment-naive RA patients, collected from the Longitudinal Health Insurance Database, were enrolled from 2000 to 2012 and followed up monthly until secondary cataracts were detected but no later than Dec 31, 2013. All participants were split into two groups according to the usage of HCQ in one year: the HCQ group (465 patients), with a usage duration higher than 90 days, and the non-HCQ group (465 patients), with a usage duration less than 30 days. The HCQ and non-HCQ groups were age-, sex-, complication- and drug combination-matched. There was no significant difference in survival rate between the two groups (p > 0.05). A multivariate logistic regression model was applied. Of all participants, 173 were diagnosed with secondary cataracts in both the HCQ and non-HCQ groups, with 28.8/1000 and 36.5/1000 person-years, respectively. After adjustments for other predictors, patients in the HCQ group had no increased (or decreased/equal) hazard of secondary cataract (hazard ratio (HR): 1.17; confidence interval (CI): 0.86–1.59; p > 0.05). HR analysis of HCQ usage duration, age, sex and corticosteroids showed that the CI of the adjusted HR was not statistically significant. This study showed that HCQ usage was not associated with the risk of cataracts in RA patients.

Abstract Background Previous research has found different multimorbidity patterns that negatively affects health outcomes of older adults. However, there is scarce evidence, especially on the role of social participation in the association between multimorbidity patterns and depression. Our study aimed to explore the relationship between multimorbidity patterns and depression among older adults in Taiwan, including the social participation effect on the different multimorbidity patterns. Methods Data were retracted from the Taiwan longitudinal study on ageing (TLSA) for this population-based cohort study. 1,975 older adults (age > 50) were included and were followed up from 1996 to 2011. We used latent class analysis to determine participants’ multimorbidity patterns in 1996, whereas their incident depression was determined in 2011 by CES-D. Multivariable logistic regression was used to analyse the relationship between multimorbidity patterns and depression. Results The participants’ average age was 62.1 years in 1996. Four multimorbidity patterns were discovered through latent class analysis, as follows: (1) Cardiometabolic group (n = 93), (2) Arthritis-cataract group (n = 105), (3) Multimorbidity group (n = 128) and (4) Relatively healthy group (n = 1649). Greater risk of incident depression was found among participants in the Multimorbidity group (OR: 1.62; 95% CI: 1.02–2.58) than the Relatively healthy group after the multivariable analysis. Compare to participants in the relatively healthy group with social participation, participants in the arthritis-cataract group without social participation (OR: 2.22, 95% CI: 1.03–4.78) and the multimorbidity group without social participation (OR: 2.21, 95% CI: 1.14–4.30) had significantly increased risk of having depression. Conclusion Distinct multimorbidity patterns among older adults in Taiwan are linked with the incident depression during later life, and social participation functioned as a protective factor.

Background and Objectives: The risks of uveitis development among pediatric patients with Down syndrome (DS) remain unclear. Therefore, we aimed to determine the risk of uveitis following a diagnosis of DS. Materials and Methods: This multi-institutional retrospective cohort study utilized the TriNetX database to identify individuals aged 18 years and younger with and without a diagnosis of DS between 1 January 2000 and 31 December 2023. The non-DS cohort consisted of randomly selected control patients matched by selected variables. This included gender, age, ethnicity, and certain comorbidities. The main outcome is the incidence of new-onset uveitis. Statistical analysis of the uveitis risk was reported using hazard ratios (HRs) and 95% confidence intervals (CIs). Separate analyses of the uveitis risk among DS patients based on age groups and gender were also performed. Results: A total of 53,993 individuals with DS (46.83% female, 58.26% white, mean age at index 5.21 ± 5.76 years) and 53,993 non-DS individuals (45.56% female, 58.28% white, mean age at index 5.21 ± 5.76 years) were recruited from the TriNetX database. Our analysis also showed no overall increased risk of uveitis among DS patients (HR: 1.33 [CI: 0.89–1.99]) compared to the non-DS cohort across the 23-year study period. Subgroup analyses based on different age groups showed that those aged 0–1 year (HR: 1.36 [CI: 0.68–2.72]), 0–5 years (HR: 1.34 [CI: 0.75–2.39]), and 6–18 years (HR: 1.15 [CI: 0.67–1.96]) were found to have no association with uveitis risk compared to their respective non-DS comparators. There was also no increased risk of uveitis among females (HR: 1.49 [CI: 0.87–2.56]) or males (HR: 0.82 [CI: 0.48–1.41]) with DS compared to their respective non-DS comparators. Conclusions: Our study found no overall increased risk of uveitis following a diagnosis of DS compared to a matched control population.

The delineation of biomarkers and neuropsychiatric symptoms across normal cognition, mild cognitive impairment (MCI), and dementia stages holds significant promise for early diagnosis and intervention strategies. This research investigates the association of neuropsychiatric symptoms, evaluated via the Neuropsychiatric Inventory (NPI), with cerebrospinal fluid (CSF) biomarkers (Amyloid-β42, P-tau, T-tau) across a spectrum of cognitive states to enhance diagnostic accuracy and treatment approaches. Drawing from the National Alzheimer’s Coordinating Center’s Uniform Data Set Version 3, comprising 977 individuals with normal cognition, 270 with MCI, and 649 with dementia. To assess neuropsychiatric symptoms, we employed the NPI to understand the behavioral and psychological symptoms associated with each cognitive category. For the analysis of CSF biomarkers, we measured levels of Amyloid-β42, P-tau, and T-tau using the enzyme-linked immunosorbent assay (ELISA) and Luminex multiplex xMAP assay protocols. These biomarkers are critical in understanding the pathophysiological underpinnings of Alzheimer’s disease and its progression, with specific patterns indicative of disease stage and severity. This study cohort consists of 1896 participants, which is composed of 977 individuals with normal cognition, 270 with MCI, and 649 with dementia. Dementia is characterized by significantly higher NPI scores, which are largely reflective of mood-related symptoms (p < 0.001). In terms of biomarkers, normal cognition shows median Amyloid-β at 656.0 pg/mL, MCI at 300.6 pg/mL, and dementia at 298.8 pg/mL (p < 0.001). Median P-tau levels are 36.00 pg/mL in normal cognition, 49.12 pg/mL in MCI, and 58.29 pg/mL in dementia (p < 0.001). Median T-tau levels are 241.0 pg/mL in normal cognition, 140.6 pg/mL in MCI, and 298.3 pg/mL in dementia (p < 0.001). Furthermore, the T-tau/Aβ-42 ratio increases progressively from 0.058 in the normal cognition group to 0.144 in the MCI group, and to 0.209 in the dementia group (p < 0.001). Similarly, the P-tau/Aβ-42 ratio also escalates from 0.305 in individuals with normal cognition to 0.560 in MCI, and to 0.941 in dementia (p < 0.001). The notable disparities in NPI and CSF biomarkers among normal, MCI and Alzheimer’s patients underscore their diagnostic potential. Their combined assessment could greatly improve early detection and precise diagnosis of MCI and dementia, facilitating more effective and timely treatment strategies.

Abstract The bidirectional relationship between obstructive sleep apnea (OSA) and diabetes mellitus (DM) has been explored in several studies. O’Connor-Reina et al., published a paper entitled: “Risk of diabetes in patients with sleep apnea: comparison of surgery versus CPAP in a long-term follow-up study” to examine a cohort study comparing the effects of surgery and continuous positive airway pressure (CPAP) on the risk of diabetes in patients with OSA. The study findings suggest that both therapies offer protection against diabetes, with upper airway surgery demonstrating better preventive efficacy than CPAP. However, potential biases and confounding variables should be considered, such as race, ethnicity, socioeconomic factors, BMI, glucose levels, HbA1c values, medication use and healthy dietary habits. Besides using International Classification of Diseases codes, the definition of DM as an outcome can also incorporate specific laboratory indicators and the use of diabetes treatment medications. Furthermore, subgroups analysis defined by demographic variables, such as age, sex, and race is recommended. The limitations of the study also include potentially data omissions due to reliance on electronic medical records from specific healthcare institutions. To enhance research comprehensiveness, alternative data sources and collaborations with additional healthcare institutions are suggested for future investigations.

Objectives Head-to-head clinical trials are common in psoriasis, but scarce in psoriatic arthritis (PsA), making treatment comparisons between therapeutic classes difficult. This study describes the relative effectiveness of targeted synthetic (ts) and biologic (b) disease-modifying antirheumatic drugs (DMARDs) on patient-reported outcomes (PROs) through network meta-analysis (NMA).Design A systematic literature review (SLR) was conducted in January 2020. Bayesian NMAs were conducted to compare treatments on Health Assessment Questionnaire Disability Index (HAQ-DI) and 36-item Short Form (SF-36) Health Survey including Mental Component Summary (MCS) and Physical Component Summary (PCS) scores.Data sources Ovid MEDLINE (including Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily),Embase and Cochrane Central Register of Controlled Trials.Eligibility criteria Phase III randomised controlled trials (RCTs) evaluating patients with PsA receiving tsDMARDS, bDMARDs or placebo were included in the SLR; there was no restriction on outcomes.Data extraction and synthesis Two independent researchers reviewed all citations. Data for studies meeting all inclusion criteria were extracted into a standardised Excel-based form by one reviewer and validated by a second reviewer. A third reviewer was consulted to resolve any discrepancies, as necessary. Risk of bias was assessed using the The National Institute for Health and Care Excellence clinical effectiveness quality assessment checklist.Results In total, 26 RCTs were included. For HAQ-DI, SF-36 PCS and SF-36 MCS scores, intravenous tumour necrosis factor (TNF) alpha inhibitors generally ranked higher than most other classes of therapies available to treat patients with PsA. For almost all outcomes, several interleukin (IL)-23, IL-17A, subcutaneous TNF and IL-12/23 agents offered comparable improvement, while cytotoxic T-lymphocyte-associated antigen 4, phosphodiesterase-4 and Janus kinase inhibitors often had the lowest efficacy.Conclusions While intravenous TNFs may provide some improvements in PROs relative to several other tsDMARDs and bDMARDs for the treatment of patients with PsA, differences between classes of therapies across outcomes were small.

Background: The impact of inhaled corticosteroid (ICS) in the interaction between asthma, COVID-19 and COVID-19 associated outcomes remain largely unknown. The objective of this study is to investigate the risk of COVID-19 and its related outcomes in patients with asthma using and not using inhaled corticosteroid (ICS).Methods: We used the TriNetX Network, a global federated network that comprises 55 healthcare organizations (HCO) in the United States, to conduct a retrospective cohort study. Patients with a diagnosis of asthma with and without ICS between January 2020 and December 2022 were included. Propensity score matching was used to match the case cohorts. Risks of COVID-19 incidence and medical utilizations were evaluated.Results: Out of 64,587 asthmatic patients with ICS and without ICS, asthmatic patients with ICS had a higher incidence of COVID-19 (Hazard ratio, HR: 1.383, 95% confidence interval, CI: 1.330–1.437). On the contrary, asthmatic patients with ICS revealed a significantly lower risk of hospitalization (HR: 0.664, 95% CI: 0.647–0.681), emergency department visits (HR: 0.774, 95% CI: 0.755–0.793), and mortality (HR:0.834, 95% CI:0.740–0.939). In addition, subgroup or sensitivity analyses were also conducted to examine the result of different vaccination status, disease severity, or COVID-19 virus variants.Conclusion: For asthmatic patients using ICS, risk of COVID-19 was significantly higher than non-users. The observed association could provide potential guidance for primary care physicians regarding the risk of COVID-19 in asthmatic patients.

The co-occurrence of psoriasis (PsO) and vitiligo is rare in Asian countries, especially in children. This case report presents the first-ever occurrence of PsO combined with vitiligo in an Asian boy under 6 years of age, in whom symptom improvement was observed after the use of methotrexate (MTX) as the sole treatment. Although previous studies have indicated that there is a close correlation between the two diseases, methotrexate (MTX), which is a commonly used treatment for PsO, is not a standard treatment for vitiligo. Even with advanced progress in biologics and Janus kinase inhibitor (JAKi), the biologics and JAKi used in vitiligo are still inconsistent. In our case report, the successful use of MTX indicated that there are shared immune pathways between PsO and vitiligo. Further exploration is needed to optimize the treatment options for this co-occurrence of PsO and vitiligo.

IntroductionCoronavirus disease 2019 (COVID-19) has caused more than 690 million deaths worldwide. Different results concerning the death rates of the Delta and Omicron variants have been recorded. We aimed to assess the secular trend of case fatality rate (CFR), identify risk factors associated with mortality following COVID-19 diagnosis, and investigate the risks of mortality and hospitalization during Delta and Omicron waves in the United States.MethodsThis study assessed 2,857,925 individuals diagnosed with COVID-19 in the United States from January 2020, to June 2022. The inclusion criterion was the presence of COVID-19 diagnostic codes in electronic medical record or a positive laboratory test of the SARS-CoV-2. Statistical analysis was bifurcated into two components, longitudinal analysis and comparative analysis. To assess the discrepancies in hospitalization and mortality rates for COVID-19, we identified the prevailing periods for the Delta and Omicron variants.ResultsLongitudinal analysis demonstrated four sharp surges in the number of deaths and CFR. The CFR was persistently higher in males and older age. The CFR of Black and White remained higher than Asians since January 2022. In comparative analysis, the adjusted hazard ratios for all-cause mortality and hospitalization were higher in Delta wave compared to the Omicron wave. Risk of all-cause mortality was found to be greater 14–30 days after a COVID-19 diagnosis, while the likelihood of hospitalization was higher in the first 14 days following a COVID-19 diagnosis in Delta wave compared with Omicron wave. Kaplan–Meier analysis revealed the cumulative probability of mortality was approximately 2-fold on day 30 in Delta than in Omicron cases (log-rank p

Abstract The incidence of gout arthritis in patients with thalassemia and the association between them was indefinite. We aimed to give epidemiological evidence regarding the association between thalassemia and gout arthritis. This retrospective cohort study extracted data relating to the risk of gout arthritis from patients diagnosed with thalassemia between 2000 and 2013. We selected the control group at a ratio of 1:4 by propensity score matching (PSM). Univariable and multivariable Cox proportional hazard regression models were performed to analyze the association between thalassemia and gout arthritis and to evaluate the hazard ratio (HR) of gout arthritis after exposure with thalassemia. The sensitivity analysis was performed to avoid the mislabeled thalassemia disease, the transfusion-dependent thalassemia was classified to compare the risk of gout arthritis. The secondary outcome for the risk of gout arthritis with antigout drugs treatment was also evaluated between study groups. In the age and sex matched cohort, the majority of thalassemia patients were women (62.03%) and aged younger than 30 years old (44.79%). There were 138 (4.2%) and 500 (3.8%) incident cases of gout arthritis in the thalassemia and non-thalassemia group. After PSM, the incidence rate, per 100 person-years, of gout arthritis was 0.48 (95% CI 0.42 to 0.56) and 0.60 (95% CI 0.51 to 0.72) in non-thalassemia individuals and patients with thalassemia, respectively. In the Cox proportional hazard regression, patients with thalassemia had no significant increase in the risk of gout arthritis (adjusted HR, 1.00; 95%CI: 0.80 to 1.25) after adjusting demographic variables and comorbidities. The Kaplan–Meier curve showed that the cumulative incidence of gout arthritis was not a significant difference in the thalassemia group than in the comparison group (p > 0.05). The sensitivity analysis showed the consistent results about the risk of gout arthritis in patients with thalassemia. Our study indicated that there was no significant increase in the risk of gout arthritis in subjects with thalassemia.Future research needs to clarify the biological mechanisms behind this connection.

Abstract Background Previous studies have shown systemic lupus erythematosus (SLE) patients had a significantly higher prevalence of thyroid diseases and hypothyroidism than matched controls, and some case reports showed SLE may occur after Hashimoto’s thyroiditis (HT). Objective This study aimed to investigate the subsequent risk of SLE in patients with HT. Methods In this retrospective cohort study done by the Taiwan National Health Insurance Research Database, the HT group (exposure group) and the non-HT group (comparator group) were propensity score matched at a ratio of 1:2 by demographic data, comorbidities, medications, and the index date. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Several sensitivity analyses were done for cross-validation of our findings. Results We identified 15,512 HT patients and matched 31,024 individuals. The incidence rate ratio of SLE was 3.58 (95% CI, 2.43–5.28; p < 0.01). Several sensitivity analyses show adjusted hazard ratio (aHR) (CIs) of 4.35 (3.28–5.76), 4.39 (3.31–5.82), 5.11 (3.75–6.98), and 4.70 (3.46–6.38), consistent with the results of the main model. Conclusion Our study showed an increased risk of SLE in the HT group after adjustment for baseline characteristics, comorbidities, and medical confounders compared with the reference group.

Abstract Background Gouty arthritis (GA) is a chronic systemic disease with recurrent acute monoarthritis. In a previous study, a higher incidence of acute flares was observed during the initial marked decrease in serum urate level. Our study evaluated the effect of early urate-lowering therapy in patients with acute GA flares. Methods This study included 40 patients with acute GA; of them, 20 received colchicine 0.5 mg colchicine twice daily, while 20 received probenecid 500 mg and colchicine 0.5 mg twice daily. We evaluated GA severity and laboratory data for 2 weeks after the initial therapy. Medians and interquartile ranges (IQRs) were calculated to evaluate clinical presentations between these two groups. Results Rapidly decreasing median serum uric acid levels was found in the patients treated with probenecid and colchicine compared with the patients treated with colchicine alone on day 8 (− 1.9 [IQR, − 3.7 to 0] vs 0.8 [IQR, − 0.1–2.2]; P

Abstract Aims/Introduction The global incidence of adolescents with type 2 diabetes mellitus is increasing. This cohort study was conducted aiming to describe the characteristics, drug‐use condition, and long‐term outcomes of adolescents with type 2 diabetes mellitus. Materials and Methods Two thousand seven hundred fifty‐five newly diagnosed adolescents with type 2 diabetes mellitus (using ICD‐9‐CM: 250.x and having ≥3 clinic visits) were identified from the national health insurance dataset during 2000–2014. Treatments were classified into four groups: metformin, sulfonylurea (SU), metformin plus SU, and insulin with or without oral antidiabetic drugs. The multiple Cox regression model was used to compare the risks of mortality and hospitalization among these four groups. Results The mean follow‐up period was 5.4 years. After 1 year of antidiabetic treatment, they gradually needed intensified therapy, and at 3 years, half of them showed treatment failure. The mortality rate was 2.08 per 1,000 person‐years. Respiratory diseases (36.2%) and dysglycemia (16.4%) were the most common causes of hospitalization among these adolescents. Compared with persons taking metformin plus SU, metformin users were associated with a lower risk of all‐cause hospitalization [0.82 (0.67–0.99)]; insulin users were associated with a higher risk of dysglycemia [4.38 (2.14–8.96)], cancer [3.76 (1.39–10.1)], and respiratory hospitalization [1.66 (1.14–2.41)]; and SU users were associated with a higher risk of hospitalization for respiratory diseases [1.91 (1.13–3.23)]. Conclusions This nationwide cohort study demonstrated that adolescents with type 2 diabetes mellitus were prone to treatment failure. Furthermore, respiratory diseases and dysglycemia were the most common causes of hospitalization.

Abstract Introduction People with dementia have high rates of hospitalization, and a share of these hospitalizations might be avoidable with appropriate ambulatory care, also known as potentially preventable hospitalization (PAH). This study investigates the associations between continuity of care and healthcare outcomes in the following year, including all-cause hospitalization, PAHs, and healthcare costs in patients with dementia. Methods This is a longitudinal retrospective cohort study of 69,658 patients with dementia obtained from the Taiwan National Health Insurance Research Database. The Continuity of Care Index (COCI) was calculated to measure the continuity of dementia-related visits across physicians. The PAHs were classified into five types as defined by the Medicare Ambulatory Care Indicators for the Elderly (MACIEs). Logistic regression models were used to examine the effect of COCI on all-cause hospitalizations and PAHs, while generalized linear models were used to analyze the effect of COCI on outpatient, hospitalization, and total healthcare costs. Results The high COCI group was significantly associated with a lower likelihood of all-cause hospitalization than the low COCI group (OR = 0.848, 95%CI: 0.821–0.875). The COCI had no significant effect on PAHs but was associated with lower outpatient costs (exp(β) = 0.960, 95%CI: 0.941 ~ 0.979), hospitalization costs (exp(β) = 0.663, 95%CI: 0.614 ~ 0.717), total healthcare costs (exp(β) = 0.962, 95%CI: 0.945–0.980). Conclusion Improving continuity of care for dementia-related outpatient visits is recommended to reduce hospitalization and healthcare costs, although there was no statistically significant effect of continuity of care found on PAHs.

Objectives We aimed to investigate the role of rheumatoid arthritis (RA) with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) exposure in COVID-19 outcomes.Methods Our study retrieved data from the US Collaborative Network in TriNetX between 1 January 2018 and 31 December 2022. We investigated b/tsDMARD use for RA: interleukin 6 inhibitor (IL-6i), Janus-associated kinase inhibitors (JAKi) or tumour necrosis factor-alpha inhibitors (TNFi, reference group). The outcomes of COVID-19 were the incidence of infection and adverse outcomes (hospitalisation, critical care services, mechanical ventilation and mortality). The HR and 95% CI of the outcomes were calculated between propensity score-matched (PSM) patients with different b/tsDMARDs.Results After PSM, 2676 JAKi vs 2676 TNFi users and 967 IL-6i vs 967 TNFi users were identified. As for COVID-19 incidence, JAKi users did not reach statistical significance (HR: 1.058, 95% CI: 0.895 to 1.250) than TNFi users. RA with JAKi users had a significant risk for hospitalisation (HR: 1.194, 95% CI: 1.003 to 1.423), mortality (HR: 1.440, 95% CI: 1.049 to 1.976) and composite adverse outcomes (HR: 1.242, 95% CI: 1.051 to 1.468) compared with TNFi users. Mortality risk tended to be significantly higher in the JAKi group without COVID-19 vaccination (HR: 1.511, 95% CI: 1.077 to 2.121). IL-6i users compared with TNFi users did not have the above findings.Conclusions RA with JAKi users had a significant risk for hospitalisation, mortality or composite adverse outcomes, especially higher mortality among those without COVID-19 vaccination. COVID-19 vaccination should be encouraged in these target cohorts. When using JAKi for patients with RA, clinicians should be vigilant about these adverse outcomes to prevent their occurrence or detect them early for early intervention.

Objectives: To investigate the association between traditional Chinese medicine (TCM) therapy and the risk of pneumonia in patients with systemic lupus erythematosus (SLE).Methods: This population-based control study analyzed the data retrieved from the National Health Insurance Research database in Taiwan. From a cohort of 2 million records of the 2000–2018 period, 9,714 newly diagnosed patients with SLE were initially included. 532 patients with pneumonia and 532 patients without pneumonia were matched 1:1 based on age, sex, and year of SLE diagnosis using propensity score matching. The use of TCM therapy was considered from the SLE diagnosis date to the index date and the cumulative days of TCM therapy were used to calculate the dose effect. Conditional logistic regression was used to investigate the risk of pneumonia infection. Furthermore, to explore the severity of pneumonia in SLE, sensitivity analyses were performed after stratification using the parameters of emergency room visit, admission time, and antibiotic use.Results: TCM therapy for >60 days could significantly reduce the risk of pneumonia in patients with SLE (95% CI = 0.46–0.91; p = 0.012). Stratified analysis showed that TCM use also reduced the risk of pneumonia in younger and female patients with SLE by 34% and 35%, respectively. TCM for >60 days significantly reduced the risk of pneumonia in the follow-up periods of >2, >3, >7, and >8 years. In addition, the exposure of TCM for >60 days reduced the risk of pneumonia in patients with SLE who were treated with antibiotics for moderate or severe pneumonia. Finally, the study found that using formulae to tonify the kidney for more than 90 days and formulae to activate blood circulation for less than 30 days could significantly reduce the risk of pneumonia infection in patients with SLE.Conclusion: TCM use is associated with a lower risk of pneumonia among patients with SLE.

Abstract Epidemiological study shows inconsistent results in the association between endometriosis and Systemic lupus erythematosus (SLE). We conducted a nationwide retrospective cohort study and analyzed data from the Taiwan Longitudinal Health Insurance Research Database 2000 (n = 958,349) over a 13-year follow-up period (2000–2013). After matching 1930 SLE women with 7720 non-SLE women in a 1:4 ratio by age, we used Cox proportional hazard regression to calculate the adjusted hazard ratio (aHR) for endometriosis diagnosed after SLE. We also used a diagnosis of endometriosis with previous gynecologic surgery codes as secondary outcomes and performed sensitivity analyses using a landmark analysis. After adjustment for age, urbanization, income, length of hospital stay, and comorbidities in the age-matched group, women with SLE had a higher risk of endometriosis than women without SLE (aHR 1.32, 95% CI 1.02–1.70). When we defined endometriosis as patients with an ICD-9 endometriosis code after undergoing gynecologic surgery, the increased risk of endometriosis in patients with SLE was not significant. Our findings suggest that the risk of endometriosis was significantly elevated in the cohort of women with SLE compared with the age-matched general cohort of women. The burden of endometriosis in SLE patients requires special attention.

Abstract Background Breast cancer is an umbrella term referring to a group of biologically and molecularly heterogeneous diseases originating from the breast. Globally, incidences of breast cancer has been increasing dramatically over the past decades. Analyses of multiple clinical “big data” can aid us in clarifying the means of preventing the disease. In addition, predisposing risk factors will be the most important issues if we can confirm their relevance. This study aims to provide an overview of the predisposing factors that contribute to a higher possibility of developing breast cancer and emphasize the signs that we ought to pay more attention to. Methods This is a matched nested case-control study. The cohort focused on identifying the eligible risk factors in breast cancer development by data screening (2000-2013) from the Taiwan National Health Insurance Research Database (NHIRD) under approved protocol. A total of 486,069 females were enrolled from a nationwide sampled database, and 3281 females was elligible as breast cancer cohort, 478,574 females who had never diagnosed with breast cancer from 2000 to 2013 were eligible as non-breast cancer controls, and matched to breast cancer cases according to age using a 1:6 ratio. Results We analyzed 3281 breast cancer cases and 19,686 non-breast cancer controls after an age-matched procedure. The significant predisposing factors associated with breast cancer development including obesity, hyperlipidemia, thyroid cancer and liver cancer. As for patients under the age of 55, gastric cancer does seem to have an impact on the development of breast cancer; compared with their counterparts over the age of 55, endometrial cancer appears to exhibit an evocative effect. Conclusions In this nationwide matched nested case-control study, we identified obesity, hyperlipidemia, previous cancers of the thyroid, stomach and liver as risk factors associated with breast cancer. However, the retrospective nature and limited case numbers of certain cancers still difficult to provide robust evidence. Further prospective studies are necessitated to corroborate this finding in order to nip the disease in the bud. Trial registration The studies involving human participants were reviewed and approved by the China Medical University Hospital [CMUH104-REC2-115(AR-4)].

BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental problem that presents with limited interests, repetitive behaviors, and deficits in reciprocal communication and social interactions. Mounting evidence indicates that an imbalanced gut microbiota contributes to autism via the gut-brain axis. Constipation may result in alteration of the gut microbiota. The clinical influence of constipation on ASD has not been fully researched. Thus, in this study we aimed to evaluate whether early childhood constipation influenced the risk of developing ASD using a nationwide population-based cohort study.MethodsWe identified 12,935 constipated children aged 3 years or younger from the National Health Insurance Research Database (NHIRD) in Taiwan from 1997 to 2013. Non-constipated children were also selected from the database and propensity score matching of age, gender, and underlying comorbidities was conducted with a ratio of 1:1. Kaplan–Meier analysis was applied to determine different levels of constipation severity and cumulative incidence of autism. Subgroup analysis was also applied in this study.ResultsThe incidence rate of ASD was 12.36 per 100,000 person-months in the constipation group, which was higher than the rate of 7.84 per 100,000 person-months noted in the non-constipation controls. Constipated children had a significantly higher risk of autism when compared to the non-constipation group (crude relative risk = 1.458, 95% CI = 1.116–1.904; adjusted hazard ratio = 1.445, 95% CI = 1.095–1.907).Moreover, among constipated children, a higher number of laxative prescriptions, male gender, constipation during infancy, and atopic dermatitis were significantly associated with higher risks of ASD when compared to the non-constipation group.ConclusionConstipation in early childhood was correlated with a significantly increased risk of ASD. Clinicians should pay attention to the possibility of ASD in constipated children. Further research is necessary to study the possible pathophysiological mechanisms of this association.

Abstract Modest drinking has been repeatedly discussed in scientific papers as protective against certain diseases, such as cardiovascular diseases, but in most cases, alcohol worsens health conditions, especially when consumed at high risk levels. The complexity of the risk relationship between alcohol and health conditions has confused clinicians as to whether it should be recommended. The study aims to balance the risks and benefits of modest drinking. This retrospective cohort study of 430,016 adults recruited from a standard health-screening program since 1994, with 11,031 deaths identified as of 2008. Drinking distinguished “modest drinker” (no more than one drink a day) from “regular drinker”. Mortality risks including all-cause mortality and diseases-specific mortality with hazard ratio (HR) were calculated by adjusting for 15 confounders. Life table was used for life expectancy. Risk predictors were subjected to Cox proportional hazards regression analysis to identify significant predictors in multivariate models and life expectancy analysis. Nearly one out of 4 males (23%) was a modest drinker, who gained 0.94 year (95% CI 0.65–1.23 year) in life over non-drinker and had 8% reduction in adjusted all-cause mortality (HR 0.92, 95% CI 0.86–0.97). In contrast, regular drinkers had 43% increase in overall mortality (HR 1.43, CI 1.35–1.52) and shortened life by 6.9 years (95% CI 6.6–7.1 years). As most drinkers also smoked, 59% in modest and 75% in regular, the combined effect shortened life by 2.0 years (95% CI 1.6–2.4 years) in modest drinker and 10.3 years (95% CI 9.8–10.7 years) in regular drinker. Cancer were increased in modest drinkers for oral (HR 2.35, CI 1.38–4.01) and esophageal (HR 3.83, CI 1.90–7.73) cancer. The gain of one year by modest drinkers was erased by a two to fourfold increase in oral and esophageal cancer and that drinking beyond modest amount led to a large loss of life expectancy. Given that drinkers are prone to cross the line of drinking, clinicians should balance the risks and benefits of drinking, as well as the understanding of whether the patient is at risk for addiction.

Abstract Background Dementia indicates a significant disease burden worldwide with increased population aging. This study aimed to investigate the impact of alcohol consumption on the risk of cognitive impairment in older adults. Methods Participants ≥ 60 years were administered the Digit Symbol Substitution Test (DSST) to evaluate cognitive function in National Health and Nutrition Examination Survey (NHANES) cycles from 1999 to 2002 and 2011 to 2014 for enrollment in the present study. Participants were categorized into non-drinker, drinker, and heavy drinker groups. Logistic regression analyses were performed to explore associations between cognitive impairment and alcohol consumption. Results Multivariate analysis showed that older adults, men, people from minority races, persons with lower education or income levels, social difficulties, hypertension, or chronic kidney disease were significantly associated with a higher risk of cognitive impairment (all p

Abstract Background Corticosteroid injection for knee osteoarthritis is limited by its modest duration of treatment effect. The liposome formulation of dexamethasone sodium phosphate (TLC599) was developed for the sustained relief of osteoarthritis pain. This clinical study was conducted to evaluate the efficacy and safety of TLC599 at two dose levels in patients with knee osteoarthritis. Methods A randomized, double-blinded, placebo-controlled study was conducted in 75 patients with osteoarthritis of the knee from 13 study centers. Patients were randomized and administered a single intra-articular injection of TLC599 or placebo and assessed for efficacy and safety for 24 weeks. Patient-reported outcomes included the Western Ontario and McMaster Universities Arthritis (WOMAC) Index for pain and function and visual analog scale for pain. Results TLC599 at 12 mg demonstrated significantly greater reduction in WOMAC pain through 12 weeks (least squares (LS) mean difference = − 0.37, p = 0.0027) and through 24 weeks (LS mean difference = − 0.35, p = 0.0037) when compared to placebo. TLC599 12 mg also exhibited significantly greater improvement in function when compared to placebo at 24 weeks (LS mean difference = − 0.26, p = 0.0457). TLC599 18 mg did not significantly improve pain or function in comparison with placebo. The use of acetaminophen during the study was less in both TLC599 groups in comparison with placebo. No major or unexpected safety issues were reported. Conclusions In participants with symptomatic knee osteoarthritis, TLC599 is a well-tolerated treatment that reduces pain and improves function for up to 24 weeks, a longer duration than that reported for existing IA treatments. Trial registration ClinicalTrials.gov , NCT03005873 . Registered on 29 December 2016

Abstract Persons with type 2 diabetes (T2D) have neutrophil dysfunction with a higher risk of infection than those without diabetes. We conducted this study aiming to compare the risk of pneumonia between metformin use and nonuse in persons with T2D. We identified 49,012 propensity score-matched metformin users and nonusers from Taiwan’s National Health Insurance Research Database between January 1, 2000, and December 31, 2017. We used the Cox proportional hazards model to compare the risks of pneumonia and respiratory death. The mean (SD) age of the participants was 57.46 (12.88) years, and the mean follow-up time for metformin users and nonusers was 5.47 (3.71) years and 5.15 (3.87) years, respectively. Compared with the nonuse of metformin, the adjusted hazard ratios (95% CI) for metformin use in bacterial pneumonia, invasive mechanical ventilation, and respiratory cause of death were 0.89 (0.84–0.94), 0.77 (0.73–0.82), and 0.64 (0.56–0.74), respectively. A longer cumulative duration of metformin use had further lower adjusted hazard ratios in these risks compared with nonuse. In patients with T2D, metformin use was associated with significantly lower risks of bacterial pneumonia, invasive mechanical ventilation, and respiratory cause of death; moreover, longer metformin use duration was associated with lower hazard ratios of these risks.

Abstract Background We aimed to compare cardiovascular risks among participants with T2DM with and without subsequent HTN and participants with HTN with and without subsequent T2DM. Methods From January 1, 2000, to December 31, 2018, we identified 16,236 matched pairs of T2DM participants with and without HTN (T2DM cohorts), 53,509 pairs of HTN participants with and without T2DM (HTN cohorts), and 21,158 pairs of comorbid HTN and T2DM participants with T2DM history or HTN history (comorbid cohorts) from Taiwan’s National Health Insurance Research Database. Cox proportional-hazard models were used to calculate the risk of cardiovascular disease. Results The mean follow-up time of this study was 6.75 years. Mean incident rates of coronary artery disease for T2DM cohorts, HTN cohorts, and comorbid cohorts were 16.80, 23.18, and 31.53 per 1000 person-years, respectively. The adjusted hazard ratios (HRs) (95% confidence intervals [95% CIs]) for incident coronary artery disease, stroke, and heart failure in T2DM participants with versus without HTN were 2.22 (2.07–2.37), 1.19 (1.16–1.23), and 0.92 (0.82–1.02), respectively; the adjusted HRs for HTN participants with versus without T2DM were 1.69 (1.55–1.84), 1.25 (1.21–1.30), and 0.98 (0.93–1.05), respectively; the adjusted HRs for comorbid T2DM and HTN participants with previous T2DM versus previous HTN were 2.78 (2.37–3.27), 1.20 (1.13–1.28), and 0.95 (0.88–1.03), respectively. Conclusions This nationwide cohort study demonstrated that both T2DM with subsequent HTN and HTN with subsequent diabetes were associated with higher cardiovascular disease risks.

IntroductionWe conducted this study to compare the risk of pneumonia between thiazolidinedione (TZD) use and nonuse in persons with type 2 diabetes (T2D).MethodsWe identified 46,763 propensity-score matched TZD users and nonusers from Taiwan’s National Health Insurance Research Database between January 1, 2000, and December 31, 2017. The Cox proportional hazards models were used for comparing the risk of morbidity and mortality associated with pneumonias.ResultsCompared with the nonuse of TZDs, the adjusted hazard ratios (95% CI) for TZD use in hospitalization for all-cause pneumonia, bacterial pneumonia, invasive mechanical ventilation, and death due to pneumonia were 0.92 (0.88–0.95), 0.95 (0.91–0.99), 0.80 (0.77–0.83), and 0.73 (0.64–0.82), respectively. The subgroup analysis revealed that pioglitazone, not rosiglitazone, was associated with a significantly lower risk of hospitalization for all-cause pneumonia [0.85 (0.82–0.89)]. Longer cumulative duration and higher cumulative dose of pioglitazone were associated with further lower adjusted hazard ratios in these outcomes compared to no-use of TZDs.DiscussionThis cohort study demonstrated that TZD use was associated with significantly lower risks of hospitalization for pneumonia, invasive mechanical ventilation, and death due to pneumonia in patients with T2D. Higher cumulative duration and dose of pioglitazone were associated with a further lower risk of outcomes.

BackgroundEnvironmental etiology of primary Sjögren’s syndrome (pSS), an autoimmune disease, has been proposed. This study determined whether the exposure to air pollutants was an independent risk factor for pSS.MethodsParticipants were enrolled from a population-based cohort registry. Daily average concentrations of air pollutants from 2000 to 2011 were divided into 4 quartiles. Adjusted hazard ratios (aHRs) of pSS for exposure to air pollutants were estimated in a Cox proportional regression model adjusting for age, sex, socioeconomic status, and residential areas. A subgroup analysis stratified by sex was conducted to validate the findings. Windows of susceptibility indicated years of exposure which contributed the most to the observed association. Ingenuity Pathway Analysis was used to identify underlying pathways of air pollutant-associated pSS pathogenesis, using Z-score visualization.ResultsTwo hundred patients among 177,307 participants developed pSS, with a mean age of 53.1 years at acumulative incidence of 0.11% from 2000 to 2011. Exposure to carbon monoxide (CO), nitric oxide (NO), and methane (CH4) was associated with a higher risk of pSS. Compared to those exposed to the lowest concentration level, the aHRs for pSS were 2.04 (95%CI=1.29-3.25), 1.86 (95%CI=1.22-2.85), and 2.21 (95%CI=1.47-3.31) for those exposed to high levels of CO, NO, and CH4, respectively. The findings persisted in the subgroup analysis, in which females exposed to high levels of CO, NO, and CH4 and males exposed to high levels of CO were associated with significantly great risk of pSS. The cumulative effect of air pollution on pSS was time-dependent. The underlying cellular mechanisms involved chronic inflammatory pathways including the interleukin-6 signaling pathway.ConclusionExposure to CO, NO, and CH4 was associated with a high risk of pSS, which was biologically plausible.

Allergic rhinitis (AR) is a common atopic disease worldwide, and it was found that babies with constipation in their early life might have an increased risk of atopic diseases, including AR. Furthermore, recent studies also indicate that the maternal gut microbiota may influence babies. Thus, we extended the definition of early life in utero and evaluated the association between maternal constipation and the risk of AR in their babies. Using the Longitudinal Health Insurance Database, a subset of Taiwan's National Health Insurance Research Database, we identified 102,820 constipated mothers and 102,820 matched controls between 2005 and 2015. Propensity score analysis was used to match birth year, child sex, birth weight, gestational age, mode of delivery, maternal comorbidities, and children antibiotics taken. Multiple Cox regression and subgroup analyzes were conducted to estimate the adjusted hazard ratio of childhood AR. The incidence of childhood AR was 83.47 per 1,000 person-years in constipated mothers. Adjusting children's sex, birth weight, gestational age, mode of delivery, maternal comorbidities, and children antibiotic use, the results showed that the children whose mothers had constipation had a 1.20-fold risk of AR compared to children of mothers without constipation. Maternal constipation was associated with an increased risk of AR. Therefore, it is important to pay close attention to pregnant mothers with constipation.

Background: Adequate management of diabetes in patients with liver cirrhosis can be challenging. We conducted this study to investigate the liver-related long term outcomes of alpha-glucosidase inhibitors (AGIs) in patients with diabetes and cirrhosis.Methods: From National Health Insurance Research Database (NHIRD) in Taiwan, we recruited propensity-score matched alpha-glucosidase inhibitor users and non-users from a cohort of type 2 diabetes mellitus (T2DM) with compensated liver cirrhosis between 1 January 2000, and 31 December 2017, and followed them until 31 December 2018. Cox proportional hazards models with robust sandwich standard error estimates were used to assess the risk of main outcomes for alpha-glucosidase inhibitor users versus non-users.Results: The incidence rates of mortality during follow-up were 65.56 vs. 96.06 per 1,000 patient-years for alpha-glucosidase inhibitor users and non-users, respectively. The multivariable-adjusted model shows that alpha-glucosidase inhibitor users had significantly lower risks of all-cause mortality (aHR 0.63, 95% CI 0.56–0.71), hepatocellular carcinoma (aHR 0.55, 95% CI 0.46–0.67), decompensated cirrhosis (aHR 0.74 95% CI 0.63–0.87), hepatic encephalopathy (aHR 0.72, 95% CI 0.60–0.87), and hepatic failure (aHR 0.74, 95% CI 0.62–0.88) than alpha-glucosidase inhibitor non-users. Patients who received alpha-glucosidase inhibitors for a cumulative duration of more than 364 days had significantly lower risks of these outcomes than non-users.Conclusion: Alpha-glucosidase inhibitor use was associated with a lower risk of mortality, hepatocellular carcinoma, decompensated cirrhosis, and hepatic failure in patients with diabetes and compensated cirrhosis. alpha-glucosidase inhibitors may be useful for the management of diabetes in patients with compensated liver cirrhosis. Large-scale prospective studies are required to verify our results.

ObjectivesRecent research has demonstrated the commonality of several biological markers between Kawasaki disease (KD) and juvenile idiopathic arthritis (JIA), including interleukin-1β and -6. Therefore, in this cohort study, we assessed whether KD increases the risk of JIA.MethodsThis study enrolled 7009 patients with and 56 072 individuals without KD in the period 2010–2018 from Taiwan’s National Health Insurance Research Database. On the basis of sex, age, and comorbidities, we executed propensity score matching at the ratio 1:8. The adjusted hazard ratio (aHR) for JIA was determined through multiple Cox regression. Stratified analysis and sensitivity tests were also employed.ResultsWhen adjusting for age, sex, and comorbidities, the JIA risk was noted to be 2.02-fold greater in children with KD than it was in those without (aHR: 2.02, 95% confidence interval: 1.12–3.67, p = 0.0205). The sensitivity test and subgroup analysis obtained consistent findings in the different sex and comorbidity subgroups.ConclusionChildren’s risk of JIA is higher if they have KD. Pediatricians should consider the possibility of JIA in this population. More investigations are necessary to identify the pathological mechanisms that link JIA and KD.