Supplemental materials as study methods and results. Figure S1. The study flowchart Table S1. Baseline characteristics of study subjects (before and after PSM matching) Table S2. Risk of Cardiovascular Outcomes in Patients with Bullous Pemphigoid Treated with Rituximab vs Steroids, Stratified by Duration of Follow-Up Table S3. Case number and Risk of Cardiovascular Outcomes in Patients With Bullous Pemphigoid Treated With Rituximab vs Steroids,(1 day to 1 year) Table S4. Risk of outcome (1 day to 1 year) PSM with different variables Table S5. Steroids used in this study: Detailed study design and data source are included in the supplementary file

RationaleObesity hypoventilation syndrome (OHS) is often underdiagnosed, with significant morbidity and mortality. Bicarbonate, as a surrogate of arterial carbon dioxide, has been proposed as a screening tool for OHS. Understanding the predictors of serum bicarbonate could provide insights into risk factors for OHS. We hypothesized that the bicarbonate levels would increase with an increase in body mass index (BMI), since the prevalence of OHS increases with obesity.MethodsWe used the TriNetX Research Network, an electronic health record database with de-identified clinical data from participating healthcare organizations across the United States, to identify 93,320 adults without pulmonary or advanced renal diseases who had serum bicarbonate and BMI measurements within 6 months of each other between 2017 and 2022. We used linear regression analysis to examine the associations between bicarbonate and BMI, age, and their interactions for the entire cohort and stratified by sex. We also applied a non-linear machine learning algorithm (XGBoost) to examine the relative importance of age, BMI, sex, race/ethnicity, and obstructive sleep apnea (OSA) status on bicarbonate.ResultsThis cohort population was 56% women and 72% white and 80% non-Hispanic individuals, with an average (SD) age of 49.4 (17.9) years and a BMI of 29.1 (6.1) kg/m2. The mean bicarbonate was 24.8 (2.8) mmol/L, with higher levels in men (mean 25.2 mmol/L) than in women (mean 24.4 mmol/L). We found a small negative association between bicarbonate and BMI, with an expected change of −0.03 mmol/L in bicarbonate for each 1 kg/m2 increase in BMI (p < 0.001), in the entire cohort and both sexes. We found sex differences in the bicarbonate trajectory with age, with women exhibiting lower bicarbonate values than men until age 50, after which the bicarbonate levels were modestly higher. The non-linear machine learning algorithm similarly revealed that age and sex played larger roles in determining bicarbonate levels than the BMI or OSA status.ConclusionContrary to our hypothesis, BMI is not associated with elevated bicarbonate levels, and age modifies the impact of sex on bicarbonate.

This is the Mendeley Supplementary File (including eMethods, Supplementary Tables and Supplementary Figures) of the study entitled "Human Papillomavirus Infection Increases Risk of New-Onset Prurigo Nodularis: A Multi-Center Retrospective Cohort Study Using Global and US Electronic Medical Records of TriNetX network" by Shuo-Yan Gau, Shao-Wei Lo, Yung-Fang Tu, Wen-Chieh Liao, Yu-Jung Su, Hui-Chin Chang, Torsten Zuberbier, Martin Metz and Shiu-Jau Chen for publication in the Journal of the American Academy of Dermatology.

Introduction: Limited research suggests that spinal manipulative therapy (SMT) has positive effects on balance, however few studies have explored if SMT is associated with reduced fall risk. This study will examine the relationship between SMT and fall risk in older adults with spinal pain, with the hypothesis that individuals receiving chiropractic SMT for spinal pain will have a reduced risk of falling over a 13-month follow-up compared to matched controls. Methods: A United States dataset including aggregated medical records (TriNetX, Inc.) of >112 million patients will be queried to identify adults aged ≥ 65 with spinal pain, with a data spanning 10 years prior to the query date. We will require pre/post medical examinations to bolster data completeness, and exclude individuals with a fall within the preceding three months and other major risk factors for falls. Patients will be divided into cohorts: (1) SMT provided by a chiropractor, and (2) non-SMT. We will use propensity matching to control for variables associated with fall risk (e.g., age, sex, comorbidities, medications). We will calculate the risk ratio with 95% confidence intervals and P-values for our primary outcome of and secondary outcome of limb fracture over 13-months’ follow-up, also exploring cumulative incidence and negative control outcomes. Results: We will compare key variables before and after propensity matching, report risk ratios, and display cumulative incidence.

Supplemental Data from TriNetX for manuscript entitled: "Increased Risk of Renal Disease in Patients with Hidradenitis Suppurativa" Background: Hidradenitis suppurativa (HS) has been linked to systemic comorbidities, but effects on kidney health remain underrecognized. Objective: Quantify the risk of major renal outcomes in adults with HS. Methods: Retrospective cohort study using de-identified electronic health records (2005-2025) from 102 TriNetX network institutions. Adults with HS were 1:1 propensity-matched to acne controls on age, sex, race/ethnicity, hypertension, diabetes, and nicotine dependence (231,036 pairs). Using ICD-10 codes, new-onset chronic kidney disease, acute kidney injury, end-stage renal disease, and dialysis requirement were tracked from one day post-index through available follow-up (~3 years). Cumulative incidence, risk ratios (RR), and Cox hazard ratios (HR) were calculated. Results: HS cohort with higher incidence of CKD (3.4% vs 2.9%; RR 1.16; HR 1.30), AKI (4.3% vs 3.0%; RR 1.41; HR 1.59), ESRD (0.6% vs 0.4%; RR 1.38; HR 1.54), and dialysis (0.7% vs 0.4%; RR 1.55; HR 1.73); p < 0.001. Kaplan-Meier curves indicated earlier and more frequent renal dysfunction in HS. Limitations: Observational design, diagnosis code reliance, and ~45% subjects missing data body-mass index may inflate risk estimates. Conclusion: Adults with HS face a meaningful increase in incident and progressive kidney disease, stressing the need for routine renal risk assessment in HS.

Thrombocytopenia (TCP) complicates acute coronary syndrome (ACS) management in patients undergoing percutaneous coronary intervention (PCI). While dual antiplatelet therapy (DAPT) reduces thrombotic events, it also increases bleeding risk, posing a challenge in TCP patients. Current guidelines, including ACC/AHA and ESC recommendations, provide limited guidance on optimal DAPT duration for this population, as risk stratification tools like the PRECISE-DAPT score exclude TCP. This study evaluates TCP’s impact on survival, bleeding, and hospitalization outcomes using real-world data. A retrospective cohort study was conducted using the TriNetX research database. PCI patients were stratified by TCP status, and propensity score matching (PSM) was applied across four models: Minimal Matching, Bleeding Matched (PRECISE-DAPT adjustments), Comorbidity Matched (Charlson Comorbidity Index adjustments), and Double Matched (both). The primary outcome was one-year overall survival; secondary outcomes included bleeding events and hospitalization rates. After PSM, 7,213 TCP+ and 7,213 TCP− patients were included. Mean age ranged from 69.4 to 69.7 years (p = 0.055–0.260), and male representation was 75.2%–76.8% (p = 0.044–0.191). TCP+ patients had significantly lower platelet levels (117.9–118.1 × 10³/μL vs. 230.1–237.9 × 10³/μL, p < 0.001). Despite adjustments, overall survival remained significantly worse for TCP+ patients: HR = 1.818 (p < 0.001, Minimal Matching), HR = 1.636 (p < 0.001, Bleeding Matched), HR = 1.383 (p < 0.001, Comorbidity Matched), and HR = 1.545 (p < 0.001, Double Matched). Bleeding risks were higher in models without bleeding risk adjustments, and hospitalization rates were elevated across most comparisons. These findings suggest TCP is an independent predictor of poor PCI outcomes, persisting even after adjustments for comorbidities and bleeding risk. Further research should refine DAPT strategies and explore systemic vulnerabilities contributing to TCP-related mortality.

BackgroundDespite pharmacological therapies to improve outcomes of pulmonary hypertension (PH), poor long-term survival remains. Exercised-based cardiac rehabilitation (ExCR) may be an alternative strategy to improve prognosis. Therefore, using an electronic medical record (EMR) database, the objective of this study was to compare mortality between patients with primary PH with ExCR vs. propensity-matched PH patients without ExCR.MethodsThe retrospective analysis was conducted on February 15, 2023 using anonymized data within TriNetX, a global federated health research network. All patients were aged ≥18 years with primary PH recorded in EMRs with at least 1-year follow-up from ExCR. Using logistic regression models, patients with PH with an EMR of ExCR were 1:1 propensity score-matched with PH patients without ExCR for age, sex, race, and comorbidities, and cardiovascular care.ResultsIn total, 109,736 patients with primary PH met the inclusion criteria for the control group and 784 patients with primary PH met the inclusion criteria for the ExCR cohort. Using the propensity score-matched cohorts, 1-year mortality from ExCR was proportionally lower with 13.6% (n = 101 of 744 patients) in the ExCR cohort compared to 23.3% (n = 174 of 747 patients) in the controls (OR 0.52, 95% CI 0.40–0.68).ConclusionThe present study of 1,514 patients with primary PH suggests that ExCR is associated with 48% lower odds of 1-year mortality, when compared to propensity score-matched patients without ExCR.

BackgroundGiven that atrial fibrillation (AF) s associated with a high risk of psychiatric disorders, understanding the potential benefits of catheter ablation is clinically significant. This study was conducted to examine whether catheter ablation can prevent psychiatric disorders in patients with AF.MethodsA retrospective cohort study was conducted over two years using data from the TriNetX electronic health record network. The study included adults diagnosed with AF and treated with either antiarrhythmic or rate-control medications. Participants were divided into two groups: those who underwent catheter ablation and a control group without ablation. The primary outcome measured was a composite of anxiety, depression, and insomnia occurrence within one to three years post-treatment. Secondary outcomes included individual psychiatric disorders, suicidal ideation or attempts, dementia, cerebral infarction, and atopic dermatitis (as a negative control).ResultsWe included 21,019 patients in each matched group. The ablation group demonstrated a lower risk of the primary combined outcome (hazard ratio(HR):0.873, 95% confidence interval (CI) 0.784–0.973, p

IntroductionWe conducted an extensive, sex-oriented real-world data analysis to explore the impact and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (coxibs) on cancer treatment outcomes. This is particularly relevant given the role of the COX-2/PGE2 pathway in tumor cell resistance to chemotherapy and radiotherapy.MethodsThe study applied a retrospective cohort design utilizing the TriNetX research database consisting of patients receiving cancer treatment in 2008-2022. The treated cohorts included patients who were prescribed with coxibs, aspirin or ibuprofen, while individuals in the control cohort did not receive these medicines during their cancer treatment. A 1:1 propensity score matching technique was used to balance the baseline characteristics in the treated and control cohorts. Then, Cox proportional hazards regression and logistic regression were applied to assess the mortality and morbidity risks among patient cohorts in a 5-year follow-up period.ResultsUse of coxibs (HR, 0.825; 95% CI 0.792-0.859 in females and HR, 0.884; 95% CI 0.848-0.921 in males) and ibuprofen (HR, 0.924; 95% CI 0.903-0.945 in females and HR, 0.940; 95% CI 0.917-0.963 in males) were associated with improved survival. Female cancer patients receiving aspirin presented increased mortality (HR, 1.078; 95% CI 1.060-1.097), while male cancer patients also had improved survival when receiving aspirin (HR, 0.966; 95% CI 0.951-0.980). Cancer subtype specific analysis suggests coxibs and ibuprofen correlated with survival, though ibuprofen and aspirin increased emergency department visits’ risk. Secondary analyses, despite limited by small cohort sizes, suggest that COX inhibition post-cancer diagnosis may benefit patients with specific cancer subtypes.DiscussionSelective COX-2 inhibition significantly reduced mortality and emergency department visit rates. Further clinical trials are needed to determine the optimal conditions for indication of coxibs as anti-inflammatory adjuvants in cancer treatment.

Objectives: We set out to evaluate the risk for severe coronavirus disease 2019 (COVID-19) infection and subsequent cerebrovascular disease (CVD) in the population with a prior diagnosis of CVD within the past 10 years. Methods: We utilized the TriNetX Analytics Network to query 369,563 COVID-19 cases up to December 30, 2020. We created 8 cohorts of patients with COVID-19 diagnosis based on a previous diagnosis of CVD. We measured the odds ratios, relative risks, risk differences for hospitalizations, ICU/critical care services, intubation, mortality, and CVD recurrence within 90 days of COVID-19 diagnosis, compared to a propensity-matched cohort with no prior history of CVD within 90 days of COVID-19 diagnosis. Results: 369,563 patients had a confirmed diagnosis of COVID-19 with a subset of 22,497 (6.09%) patients with a prior diagnosis of CVD within 10 years. All cohorts with a CVD diagnosis had an increased risk of hospitalization, critical care services, and mortality within 90 days of COVID-19 diagnosis. Additionally, the data demonstrate that any history of CVD is associated with significantly increased odds of subsequent CVD post-COVID-19 compared to a matched control. Conclusions: CVD, a known complication of COVID-19, is more frequent in patients with a prior history of CVD. Patients with any previous diagnosis of CVD are at higher risks of morbidity and mortality from COVID-19 infection. In patients admitted to the ED due to COVID-19 symptoms, these risk factors should be promptly identified as delayed or missed risk stratification and could lead to an ineffective and untimely diagnosis of subsequent CVD, which would lead to protracted hospitalization and poor prognosis.