Prior COVID-19 vaccination and reduced risk of cerebrovascular diseases among COVID-19 survivors.

The effects of COVID-19 vaccination on short-term and long-term cerebrovascular risks among COVID-19 survivors remained unknown. We conducted a national multi-center retrospective cohort study with 151 597 vaccinated and 151 597 unvaccinated COVID-19 patients using the TriNetX database, from January 1, 2020 to December 31, 2023. Patients baseline characteristics were balanced with propensity score matching (PSM). The outcomes were incident cerebrovascular diseases occurred between 1st and 30th days (short-term) after COVID-19 diagnosis. Nine subgroup analyses were conducted to explore potential effect modifications. We performed six sensitivity analyses, including evaluation of outcomes between 1st to 180th days, accounting for competing risk, and incorporating different variant timeline to test the robustness of our results. Kaplan-Meier curves and Log-Rank tests were performed to evaluate survival difference. Cox proportional hazards regressions were adopted to estimate the PSM-adjusted hazard ratios (HR). The overall short-term cerebrovascular risks were lower in the vaccinated group compared to the unvaccinated group (HR: 0.66, 95% CI: 0.56-0.77), specifically cerebral infarction (HR: 0.62, 95% CI: 0.48-0.79), occlusion and stenosis of precerebral arteries (HR: 0.74, 95% CI: 0.53-0.98), other cerebrovascular diseases (HR: 0.57, 95% CI: 0.42-0.77), and sequelae of cerebrovascular disease (HR: 0.39, 95% CI:0.23-0.68). Similarly, the overall cerebrovascular risks were lower in those vaccinated among most subgroups. The long-term outcomes, though slightly attenuated, were consistent (HR: 0.80, 95% CI: 0.73-0.87). Full 2-dose vaccination was associated with a further reduced risk of cerebrovascular diseases (HR: 0.63, 95% CI: 0.50-0.80) compared to unvaccinated patients. Unvaccinated COVID-19 survivors have significantly higher cerebrovascular risks than their vaccinated counterparts. Thus, clinicians are recommended to monitor this population closely for stroke events during postinfection follow-up.

Difference of Cerebrospinal Fluid Biomarkers and Neuropsychiatric Symptoms Profiles among Normal Cognition, Mild Cognitive Impairment, and Dementia Patient.

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-ß42, 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-ß42, 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-ß 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/Aß-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/Aß-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.

The impact of heavy alcohol consumption on cognitive impairment in young old and middle old persons.

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 < 0.05). In the young old (60-69 years), heavy amount of alcohol drinking was significantly associated with lower risk of cognitive impairment compared with drinkers [adjusted odds ratio (aOR): 0.280, 95% Confidence interval (CI) 0.095-0.826]. But in the middle old persons (≥ 70 years), heavy alcohol drinking was associated with higher risk of cognitive impairment (aOR: 2.929, 95% CI 0.624-13.74). CONCLUSIONS: Our study demonstrated that light to heavy drinking was associated with lower risk of cognitive impairment in participants aged between 60 and 69 years, but caution is needed in the middle old people with heavy alcohol drinking.

What affects local community hospitals' survival in turbulent times?

OBJECTIVES: Hospital closures became a prevalent phenomenon in Taiwan after the implementation of a national health insurance program. A wide range of causes contributes to the viability of hospitals, but little is known about the situation under universal coverage health systems. The purpose of present study is to recognize the factors that may contribute to hospital survival under the universal coverage health system. STUDY DESIGN: This is a retrospective case-control study. Local community hospitals that contracted with the Bureau of National Health Insurance in 1998 and remained open during the period 1998-2011 are the designated cases. Controls are local community hospitals that closed during the same period. METHODS: Using longitudinal representative health claim data, 209 local community hospitals that closed during 1998-2011 were compared with 165 that remained open. Variables related to institutional characteristics, degree of competition, characteristics of patients and financial performance were analyzed by logistic regression models. RESULTS: Hospitals' survival was positively related to specialty hospital, the number of respiratory care beds, the physician to population ratio, the number of clinics in the same region, a highly competitive market and the occupancy rate of elderly patients in the hospital. Teaching hospitals, investor-owned hospitals, the provision of obstetrics services or home care, and the number of medical centers or other local community hospitals may jeopardize the chance of survival. CONCLUSIONS: Factors-enhanced local hospitals to survive under the universal coverage health system have been identified. Hospital managers could manipulate these findings and adapt strategies for subsistence.

Prescription patterns for tuberculosis treatment and adherence to treatment guidelines: a population-based study in Taiwan.

PURPOSE: Tuberculosis is a health threat in Taiwan. Previous research is mainly focused on patients' compliance, and research on medicines prescribed by physicians is limited. This study endeavors to present the prescription patterns of Tuberculosis treatment and its adherence to the guidelines. METHODS: Newly diagnosed Tuberculosis patients in 2008 were selected from the National Health Insurance claims database. We divided prescriptions into standard prescriptions, non-standard prescriptions, and second-line medicines on the basis of the fourth edition of Taiwan's guidelines for the diagnosis and treatment of Tuberculosis. We first described the distribution of these prescriptions of TB regimen in the first 2 months among the new patients. Furthermore, a graphical presentation was used to visualize physician's complex prescription behavior. RESULTS: In total, 11,164 patients were included in this analysis; 28,291 prescriptions were prescribed during the first 2 months after diagnosis. Among these prescriptions, 53.34% were standard prescriptions, 45.81% were non-standard prescriptions, and 0.84% were second-line medicines. Prescribing medicines for 28 days at the first visit was the most common scenario. Approximately 35 patterns can be derived from the prescriptions in Taiwan. CONCLUSIONS: The prescriptions suggested in the guideline are considered to have better therapeutic effects. However, this study revealed that approximately 55% prescriptions adhered to the regimen recommended by the guidelines. The Pharmacoepidemiology and Drug Safety results of this study can help to explore possible reasons to the poor control of the disease.

Sodium-Glucose Cotransporter-2 Inhibitors and Nephritis Among Patients With Systemic Lupus Erythematosus.

Importance: Lupus nephritis is a major complication of systemic lupus erythematosus (SLE). Randomized clinical trials have shown nephroprotective and cardioprotective effects of sodium-glucose cotransporter-2 inhibitors (SGLT2is). Objective: To investigate whether the use of SGLT2is is associated with the onset and progression of lupus nephritis and other kidney and cardiac outcomes in patients with SLE and type 2 diabetes. Design, Setting, and Participants: This multicenter cohort study used the US Collaborative Network of the TriNetX clinical data platform to identify patients with SLE and type 2 diabetes from January 1, 2015, to December 31, 2022. Data collection and analysis were conducted in September 2023. Exposures: Individuals were categorized into 2 groups by SGLT2i use or nonuse with 1:1 propensity score matching. Main Outcomes and Measures: The Kaplan-Meier method and Cox proportional hazards regression models were used to calculate the 5-year adjusted hazard ratios (AHRs) of lupus nephritis, dialysis, kidney transplant, heart failure, and mortality for the 2 groups. Results: From 31 790 eligible participants, 1775 matched pairs of SGLT2i users and nonusers (N = 3550) were selected based on propensity scores. The mean (SD) age of matched participants was 56.8 (11.6) years, and 3012 (84.8%) were women. SGLT2i users had a significantly lower risk of lupus nephritis (AHR, 0.55; 95% CI, 0.40-0.77), dialysis (AHR, 0.29; 95% CI, 0.17-0.48), kidney transplant (AHR, 0.14; 95% CI, 0.03-0.62), heart failure (AHR, 0.65; 95% CI, 0.53-0.78), and all-cause mortality (AHR, 0.35; 95% CI, 0.26-0.47) than SGLT2i nonusers. Conclusions and Relevance: In this cohort study of patients with SLE and type 2 diabetes, SGLT2i users had a significantly lower risk of lupus nephritis, dialysis, kidney transplant, heart failure, and all-cause mortality than nonusers. The findings suggest that SGLT2is may provide some nephroprotective and cardioprotective benefits.

Real-World Assessment of Recommended COVID-19 Vaccination Waiting Period after Chemotherapy.

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.

Diabetic Macular Edema Is Predictive of Renal Failure in Patients With Diabetes Mellitus and Chronic Kidney Disease.

CONTEXT: Chronic hyperglycemia in patients with diabetes mellitus (DM) causes retinal damage and leakage, resulting in vision loss. Although diabetic retinopathy (DR) and diabetic kidney disease (DKD) are usually correlated, the relationship between diabetic macular edema (DME) and DKD remains unknown. OBJECTIVE: To assess whether DME presence can predict renal failure in patients with DM and chronic kidney disease (CKD). METHODS: This retrospective cohort study used data from 120 healthcare organizations in the TriNetX network. Electronic medical records of approximately 90 million patients were reviewed. The study population was classified into DME and non-DME cohorts. Primary and secondary outcomes were new-onset end-stage renal disease (ESRD) and all-cause mortality, respectively. Covariate factors were incorporated to reduce confounding effects. RESULTS: Before matching, the DME cohort used more medication and had poorer renal function and blood sugar control than the non-DME cohort. Subsequently, the 2 groups were well-matched in demographics, socioeconomic status, lifestyle, comorbidities, and medication usage. The DME cohort had a significantly higher risk of ESRD, dialysis, and renal transplantation than the non-DME cohort. Subgroup analyses showed consistent results irrespective of follow-up duration, initial estimated glomerular filtration rate, or glycated hemoglobin levels. Additionally, the DME cohort had a lower risk of all-cause mortality than the non-DME cohort. CONCLUSION: Statistically significant 5-year increased risks of ESRD, dialysis, and renal transplantation were observed in patients with concurrent DME. Therefore, close monitoring and follow-up of the renal function in DM patients with DME are necessary and strongly recommended.

Long-COVID impacts taste and olfactory in individuals with substance use disorder: A retrospective cohort study from the TriNetX US Collaborative Networks.

Substance use disorder (SUD) exacerbates the impact of Long-COVID, particularly increasing the risk of taste and olfactory disorders. Analyzing retrospective cohort data from TriNetX and over 33 million records (Jan 2020-Dec 2022), this study focused on 1,512,358 participants, revealing that SUD significantly heightens the likelihood of experiencing taste disturbances and anosmia in Long-COVID sufferers. Results indicated that individuals with SUD face a higher incidence of sensory impairments compared to controls, with older adults and women being particularly vulnerable. Smokers with SUD were found to have an increased risk of olfactory and taste dysfunctions. The findings underscore the importance of early screening, diagnosis, and interventions for Long-COVID patients with a history of SUD, suggesting a need for clinicians to monitor for depression and anxiety linked to sensory dysfunction for comprehensive care.

Tooth Loss and Chronic Pain: A Population-based Analysis of the National Health and Nutrition Examination Survey.

Poor oral health conditions in adults are associated with chronic pain. A nationwide cross-sectional study was conducted to investigate the link between tooth loss and chronic pain. The study involved 8,662 participants from the National Health and Nutrition Examination Survey. Tooth count was categorized into 4 groups, and chronic pain was defined as persistent pain lasting over 3 months despite treatment. Location of the chronic pain, demographics, comorbidities, lifestyle determinants, and dietary intake were retrieved. Univariate and multivariate logistic regression were used to explore cross-sectional associations between tooth count and chronic pain. Compared to participants with more than 20 teeth, those with severe tooth loss presented greater odds of chronic pain (adjusted odds ratio [aOR] = 2.111, 95% confidence intervals (CI) = 1.213-3.676 for patients with 1-8 teeth). Edentulous participants presented with significantly higher odds of chronic pain in the lower extremities (78.4%) and buttocks (49.5%). In the multivariate model, apart from rheumatic arthritis (aOR = 4.004, 95% CI = 2.766-5.798), variables of higher chronic pain included smoking (aOR = 1.518, 95% CI = 1.228-1.878), and hypertension (aOR = 1.463, 95% CI = 1.013-2.112). On the contrary, being Mexican American (aOR = .603, 95% CI = .414-.880) was associated with lower odds of chronic pain. The findings suggested a significant link between chronic pain and tooth loss, independent of ethnicity, lifestyle determinants, and immune-mediated inflammatory diseases including rheumatoid arthritis. PERSPECTIVE: A U.S. nationwide study examined tooth loss and chronic pain. Those with severe tooth loss had increased odds of chronic pain. Edentulous individuals presented higher odds of pain in lower extremities and buttocks. This study highlighted the link between tooth loss and chronic pain, independent of comorbidities and lifestyle factors.

Risk of dyslipidemia and major adverse cardiac events with tofacitinib versus adalimumab in rheumatoid arthritis: a real-world cohort study from 7580 patients.

Objective: To compare the effects of tofacitinib and adalimumab on the risk of adverse lipidaemia outcomes in patients with newly diagnosed rheumatoid arthritis (RA). Methods: Data 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. Results: A 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]). Conclusion: Tofacitinib 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.

Sodium-Glucose Cotransport Protein 2 Inhibitors in Patients With Type 2 Diabetes and Acute Kidney Disease.

Importance: Sodium-glucose cotransport protein 2 inhibitors (SGLT-2is) have demonstrated associations with positive kidney-related and cardiovascular outcomes in patients with type 2 diabetes. However, the association of SGLT-2is with outcomes among patients with type 2 diabetes and acute kidney disease (AKD) remains unclear. Objective: To examine the long-term associations of SGLT-2is with mortality, major adverse kidney events (MAKEs), and major adverse cardiovascular events (MACEs) in patients with type 2 diabetes and AKD. Design, Setting, and Participants: This cohort study used global health care data (the TriNetX database) spanning from September 30, 2002, to September 30, 2022. Propensity score matching was used to select a cohort of patients, and follow-up was conducted with a maximum duration of 5 years (completed on September 30, 2022) or until the occurrence of an outcome or death. Intervention: The use of SGLT-2is. Main Outcomes and Measures: The primary outcomes measured were mortality, MAKEs, and MACEs. Adjusted hazard ratios (AHR) with 95% CIs were calculated to compare the risks between SGLT-2i users and nonusers, representing the mean treatment effect among the treated patients. Results: A total of 230 366 patients with AKD (mean [SD] age, 67.1 [16.4] years; 51.8% men and 48.2% women) were enrolled in the study, which had a median follow-up duration of 2.3 (IQR, 1.2-3.5) years. Among these, 5319 individuals (2.3%) were identified as SGLT-2i users. Among nonusers, the incidence of mortality was 18.7%, the incidence of MAKEs was 21.0%, and the incidence of MACEs was 25.8%. After propensity score matching, the absolute differences between SGLT-2i users and nonusers for incidence of mortality, MAKEs, and MACEs were 9.7%, 11.5%, and 12.3%, respectively. Based on the treated population, SGLT-2i use was associated with a significantly lower risk of mortality (AHR, 0.69 [95% CI, 0.62-0.77]), MAKEs (AHR, 0.62 [95% CI, 0.56-0.69]), and MACEs (AHR, 0.75 [95% CI, 0.65-0.88]) compared with nonuse. External validation using a multicenter cohort data set of 1233 patients with AKD patients who were SGLT-2i users confirmed the observed beneficial outcomes. Notably, the risk reduction associated with SGLT-2is remained significant even among patients without hypertension, those with advanced chronic kidney disease, and those not receiving other hypoglycemic agents. Conclusions and Relevance: In this cohort study of patients with type 2 diabetes and AKD, administration of SGLT-2is was associated with a significant reduction in all-cause mortality, MAKEs, and MACEs when compared with nonuse, underscoring the importance of SGLT-2is in care after acute kidney injury. These findings emphasize the potential benefits of SGLT-2is in managing AKD and mitigating the risks of major cardiovascular and kidney diseases.

Vertical equity of healthcare in Taiwan: health services were distributed according to need.

INTRODUCTION: To test the hypothesis that the distribution of healthcare services is according to health need can be achieved under a rather open access system. METHODS: The 2001 National Health Interview Survey of Taiwan and National Health Insurance claims data were linked in the study. Health need was defined by self-perceived health status. We used Concentration index to measure need-related inequality in healthcare utilization and expenditure. RESULTS: People with greater health need received more healthcare services, indicating a pro-need character of healthcare distribution, conforming to the meaning of vertical equity. For outpatient service, subjects with the highest health need had higher proportion of ever use in a year than those who had the least health need and consumed more outpatient visits and expenditures per person per year. Similar patterns were observed for emergency services and hospitalization. The concentration indices of utilization for outpatient, emergency services, and hospitalization suggest that the distribution of utilization was related to health need, whereas the preventive service was less related to need. CONCLUSIONS: The universal coverage plus healthcare networking system makes it possible for healthcare to be utilized according to need. Taiwan's experience can serve as a reference for health reform.

Corrigendum to "Long-term cardiovascular outcomes in COVID-19 survivors among non-vaccinated population: a retrospective cohort study from the TriNetX US collaborative networks".

[This corrects the article DOI: 10.1016/j.eclinm.2022.101619.].

Metformin use before COVID-19 vaccination and the risks of COVID-19 incidence, medical utilization, and all-cause mortality in patients with type 2 diabetes mellitus.

AIMS: We designed this study to determine whether metformin use before COVID-19 vaccination influences the risk of COVID-19 infection, medical utilization, and mortality. METHODS: We used the US collaborative network of TriNetX to identify 123,709 patients with type 2 diabetes mellitus fully vaccinated against COVID-19 between January 1, 2020, and November 22, 2022. The study selected 20,894 pairs of metformin users and nonusers by propensity score matching. The Kaplan-Meier method and Cox proportional hazards models were used to compare the risks of COVID-19 infection, medical utilization, and mortality between the study and control groups. RESULTS: No significant difference was noted between metformin users and nonusers in the risk of COVID-19 incidence (aHR = 1.02, 95% CI = 0.94-1.10). Compared to the control cohort, the metformin cohort exhibited a significantly lower risk of hospitalization (aHR = 0.85, 95% CI = 0.81-0.89), critical care services (aHR = 0.81, 95% CI = 0.70-0.94), mechanical ventilation (aHR = 0.75, 95% CI = 0.60-0.95), and mortality (aHR = 0.75, 95% CI = 0.63-0.89). The subgroup analyses and sensitivity analysis showed similar results. CONCLUSION: The present study showed that metformin use before COVID-19 vaccination could not reduce COVID-19 incidence; however, it was associated with significantly lower risks of hospitalization, intensive care service, mechanical ventilation, and mortality in fully vaccinated type 2 diabetes mellitus patients.

COVID-19 outcomes in patients with rheumatoid arthritis with biologic or targeted synthetic DMARDs.

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.

Risk of autoimmune diseases in patients with COVID-19: A retrospective cohort study.

Background: There are a growing number of case reports of various autoimmune diseases occurring after COVID-19, yet there is no large-scale population-based evidence to support this potential association. This study provides a closer insight into the association between COVID-19 and autoimmune diseases and reveals discrepancies across sex, age, and race of participants. Methods: This is a retrospective cohort study based on the TriNetX U.S. Collaborative Network. In the test-negative design, cases were participants with positive polymerase chain reaction (PCR) test results for SARS-CoV-2, while controls were participants who tested negative and were not diagnosed with COVID-19 throughout the follow-up period. Patients with COVID-19 and controls were propensity score-matched (1: 1) for age, sex, race, adverse socioeconomic status, lifestyle-related variables, and comorbidities. The primary endpoint is the incidence of newly recorded autoimmune diseases. Adjusted hazard ratios (aHRs) and 95% confident intervals (CIs) of autoimmune diseases were calculated between propensity score-matched groups with the use of Cox proportional-hazards regression models. Findings: Between January 1st, 2020 and December 31st, 2021, 3,814,479 participants were included in the study (888,463 cases and 2,926,016 controls). After matching, the COVID-19 cohort exhibited significantly higher risks of rheumatoid arthritis (aHR:2.98, 95% CI:2.78-3.20), ankylosing spondylitis (aHR:3.21, 95% CI:2.50-4.13), systemic lupus erythematosus (aHR:2.99, 95% CI:2.68-3.34), dermatopolymyositis (aHR:1.96, 95% CI:1.47-2.61), systemic sclerosis (aHR:2.58, 95% CI:2.02-3.28), Sjögren's syndrome (aHR:2.62, 95% CI:2.29-3.00), mixed connective tissue disease (aHR:3.14, 95% CI:2.26-4.36), Behçet's disease (aHR:2.32, 95% CI:1.38-3.89), polymyalgia rheumatica (aHR:2.90, 95% CI:2.36-3.57), vasculitis (aHR:1.96, 95% CI:1.74-2.20), psoriasis (aHR:2.91, 95% CI:2.67-3.17), inflammatory bowel disease (aHR:1.78, 95%CI:1.72-1.84), celiac disease (aHR:2.68, 95% CI:2.51-2.85), type 1 diabetes mellitus (aHR:2.68, 95%CI:2.51-2.85) and mortality (aHR:1.20, 95% CI:1.16-1.24). Interpretation: COVID-19 is associated with a different degree of risk for various autoimmune diseases. Given the large sample size and relatively modest effects these findings should be replicated in an independent dataset. Further research is needed to better understand the underlying mechanisms. Funding: Kaohsiung Veterans General Hospital (KSVGH111-113).

Recent Human Papillomavirus Vaccination is Associated with a Lower Risk of COVID-19: A US Database Cohort Study.

OBJECTIVE: To explore the association between human papillomavirus (HPV) vaccination and risk of coronavirus disease 2019 (COVID-19). Specifically, our study aimed to test the hypothesis that HPV vaccination may also induce trained immunity, which would potentially reduce the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and improve clinical outcomes. BACKGROUND: Several vaccines have been reported to trigger non-specific immune reactions that could offer protection from heterologous infections. A recent case report showed that verruca vulgaris regressed after COVID-19, suggesting a possible negative association between COVID-19 and HPV infection. METHODS: We enrolled 57,584 women with HPV vaccination and compared them with propensity score-matched controls who never received HPV vaccination in relation to the risk of COVID-19 incidence. Cox proportional hazard regression analysis was conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses stratified by age, race, comorbid asthma, and obesity were performed. RESULTS: The risk of COVID-19 incidence was significantly lower in those who had recently received the HPV vaccine (within 1 year after HPV vaccination, aHR: 0.818, 95% CI 0.764-0.876; within 1-2 years after HPV vaccination, aHR: 0.890, 95% CI 0.824-0.961). Several limitations were recognized in this study, including residual confounding, problems of misclassification due to the use of electronic health record data, and that we were unable to keep track of the patients' HPV infection status and the HPV antibody levels in those who had received the vaccine. CONCLUSIONS: Recent HPV vaccination was associated with a lower risk of incident COVID-19 and hospitalization. Based on the promising protective effect of HPV vaccine shown in this study, these findings should be replicated in an independent dataset. Further studies are needed to provide a better understanding of the underlying mechanisms and the differences in risks among 2-, 4-, or 9-valent HPV vaccine recipients.

Associations between COVID-19 outcomes and asthmatic patients with inhaled corticosteroid.

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.