Description of TriNetX database, utilized methods and administrative codes, results of stratification and sensitivity analysis. Supplementary files of "Major Depressive Disorder, Bipolar Disorder and Schizophrenia in Patients with Prurigo Nodularis: a Multicenter Retrospective Cohort Study derived from TriNetX research network" for publication in the Journal of the American Academy of Dermatology.

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.

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

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.

This population-based cohort study performed utilizing the TriNetX database compares the risk of subsequent primary malignancies in patients diagnosed with melanoma or non-melanoma skin cancer, including basal cell carcinomas and squamous cell carcinomas. A case cohort was identified using ICD-10-CM codes for melanoma, basal cell carcinoma, and squamous cell carcinoma, as well as 11 of the most common primary malignancies as defined by the American Cancer Society. These included breast, prostate, lung, colorectal, bladder, non-Hodgkin’s lymphoma, kidney, uterine, leukemia, pancreas, and thyroid cancer.

A total of 130,526 melanoma patients and 130,526 non-melanoma skin cancer patients were identified after propensity score matching for demographics. The adjusted risk ratios revealed that melanoma patients had a significantly increased risk of developing breast, prostate, lung, kidney, pancreatic, and thyroid cancer compared to NMSC patients. No significant differences were found in the risk of developing colorectal cancer, prostate cancer, bladder cancer, non-Hodgkin’s lymphoma, or leukemia between the two groups.

Overall, this TriNetX database study underscores the importance of tailored cancer surveillance, particularly for breast, prostate, lung, kidney, pancreatic, and thyroid cancer in melanoma survivors. Future research should focus on exploring the mechanisms behind the differential cancer risks observed in this study and refining screening strategies for higher-risk populations.

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

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.

Supplemental Tables for JAAD Manuscript Titled: "Longitudinal Cardiovascular Outcomes in Pyoderma Gangrenosum: A Propensity-Matched TriNetX Cohort Study."

This supplemental material has been provided by the authors to give readers additional information about their work.

Supplemental Methods This study utilized a retrospective cohort design leveraging data from the TriNetX research network, which aggregates electronic health records (EHRs) from 97 healthcare organizations (HCOs). The analysis compared two patient cohorts based on cardiovascular disease (CVD) status, both of whom had been diagnosed with skin cancers, including malignant melanoma (ICD-10: C43), squamous cell carcinoma (C44.92), or basal cell carcinoma (C44.91), and underwent Mohs micrographic surgery (CPT: 17311). The CVD cohort included patients with a concurrent diagnosis of cardiovascular disease, including hypertension (ICD-10: I10-I15), hypertensive crisis (I16), or ischemic heart disease (I20-I25), whereas the non-CVD cohort consisted of patients with similar skin cancer diagnoses and Mohs procedures but without any history of these cardiovascular conditions. The study population was limited to patients whose diagnoses and procedures occurred between January 1, 2015, and December 31, 2023. Patients with an index event occurring more than 20 years prior to the study period were excluded. The index event was defined as the date of the first recorded visit (TNX:Visit) associated with both the skin cancer diagnosis and the Mohs micrographic surgery procedure. A follow-up visit (CVD f/u) was required within six months after the initial visit to ensure patients remained engaged with healthcare services and to capture subsequent cardiovascular events. The time window for outcomes assessment began one day after the index event and extended 30 days and 3-months postoperatively. The primary outcomes included acute myocardial infarction (AMI; ICD-10: I21) and stroke (ICD-10: I63.9). Patients who had a documented history of these outcomes before the study time window were excluded from the risk analysis and survival analysis. To minimize confounding, propensity score matching (PSM) was performed at a 1:1 ratio between the CVD and non-CVD cohorts. Matching variables included age, sex, race, ethnicity, comorbid conditions (hypertension, diabetes, chronic kidney disease, hyperlipidemia, obesity), medication use (anticoagulants, beta-blockers, lipid-lowering agents), and laboratory values (e.g., tobacco smoking status). After matching, each cohort consisted of 27,758 patients. The study employed multiple statistical approaches to compare outcomes between the cohorts. Risk analysis was performed to calculate risk differences, risk ratios, and odds ratios for AMI and stroke. Kaplan-Meier survival analysis was conducted to assess differences in survival probability, applying censoring to account for patients lost to follow-up. Number of instances analysis was used to quantify the frequency of AMI and stroke occurrences within the 30-day and 3-month time window.

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.

Background: Prior studies have observed a seasonal pattern in the incidence of both polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), but neither finding has been consistently replicated in larger cohort studies or meta-analyses. The objective of this study was to describe seasonal patterns among incident cases of GCA and PMR. Methods: A retrospective cohort study was conducted using data from the TriNetX (Cambridge, MA, USA) electronic health records database, which includes records from multiple United States health organizations. Patients with GCA were identified using validated case-finding algorithms (PPV 79%), which required (1) 2 encounters with GCA diagnostic codes (ICD-9-CM 446.5/ICD-10 M31.6 or M31.5) that occurred at least 30 days apart and (2) at least one moderate-high dose prednisone prescription (greater than or equal to 20mg/day of prednisone or one dose of 500mg or greater intravenous methylprednisolone). Patients with PMR were identified using 2 encounters with a PMR diagnostic code (ICD-9-CM 725/ICD-10 M35.3) at least 30 days apart, any dose of prednisone, and not meeting the criteria for GCA. The index date was defined as the first date of moderate-high dose prednisone for GCA and the first date of any prednisone prescription for PMR. Patients who were under 50 years of age or had less than 1 year of follow up prior to the index date were excluded. The incident rate ratio (IRR) was calculated using unconditional maximum likelihood estimations and confidence intervals were calculated using Wald normal approximation intervals. Results: We identified 1,129 cases of GCA and 17,023 incident cases of PMR who were followed for 149,005 patient-years prior to their index date of diagnosis. The mean age for incident cases of GCA was 73.9 years (SD 8.1) and the mean age for PMR was 72.3 (SD 8.5). Most patients were female (69%% GCA, 59% PMR) and reported white (79% GCA, 85% PMR) or black (10% GCA, 6% PMR) race/ethnicity. There were no significant differences in the incidence rate ratio of GCA diagnoses as compared to January-March for April-June (IRR 0.99, 95% confidence interval (CI) 0.84-1.17), July-September (IRR 1.06, CI 0.90-1.25), or October-December (IRR 1.01, CI 0.85-1.19) (Figure 1A). There were also no significant differences in the incidence rate ratio of PMR diagnoses as compared to January-March for April-June (IRR 1.00, 95% confidence interval (CI) 0.), July-0.96-1.05, September (IRR 1.00, CI 0.), or O0.96-1.05, or October-December (IRR 0.96, CI 0.92-1.00) (Figure 1A). Conclusions: In this large analysis of an electronic health records database, there were no seasonal patterns in the diagnosis of GCA or PMR. These results do not support the existence of a seasonal pattern in diagnosis for either disease but require validation in a better-characterized cohort. Disclosure: Sebastian Sattui receives research funding related to clinical trials by AstraZeneca (MANDARA). Michael Putman receives research funding related to clinical trials by Abbvie (SELECT-GCA) and AstraZeneca (MANDARA).

A retrospective cohort study was conducted using the TriNetX Global Collaborative Network, a federated database comprising de-identified electronic health records from 142 healthcare organizations (HCOs). The database was queried on March 13, 2025, to identify patients diagnosed with gastroesophageal reflux disease (GERD). Patients were stratified into two cohorts based on proton pump inhibitor (PPI) exposure. The GERD+PPI cohort included patients with a diagnosis of GERD (ICD-10: K21) who had ≥2 prescriptions for a PPI (omeprazole, esomeprazole, pantoprazole, lansoprazole, dexlansoprazole, or rabeprazole) within 5 years prior to the index date. The GERD control cohort included GERD patients with no history of PPI use, defined as no recorded prescriptions for any listed PPIs at any time. Patients were excluded in the risk analysis if they had a history of cutaneous fungal infections, including onychomycosis, tinea corporis, tinea pedis, tinea cruris, or cutaneous candidiasis. Additional exclusions included a history of systemic antifungal use (fluconazole, terbinafine, itraconazole) within 1 day prior to the index date or a history of immunodeficiency conditions, including HIV (ICD-10: B20), solid organ transplantation, or primary immunodeficiency disorders (ICD-10: D80-D84). Cohorts were propensity score-matched (1:1) to minimize confounding, using variables including age, sex, race/ethnicity, diabetes, obesity, immunosuppression, and concurrent medication use. Standardized mean differences (SMDs) were used to assess balance between matched cohorts. The primary outcome was the incidence of cutaneous fungal infections following PPI use. Risk ratios (RR) with 95% confidence intervals (CIs) were calculated using logistic regression. A p-value <0.05 was considered statistically significant. All statistical analyses were conducted within the TriNetX platform.

The effects of the COVID-19 period among people who smoke (compared by sex) are largely unknown. The purpose of this study was to compare body mass index (BMI) increase among men and women who smoked during the pandemic. We used a retrospective longitudinal, observational study design of secondary data. We used electronic health records from TriNetX network (n = 486,072) from April 13, 2020-May 5, 2022 among adults aged 18–64 who smoked and had a normal BMI prior to the pandemic. The main measure was a change of BMI from < 25 to ≥25. Risk ratio was determined between men and women with propensity score matching. Overall, 15.8% increased BMI to ≥25; 44,540 (18.3%) were women and 32,341 (13.3%) were men (Risk Ratio = 1.38, 95% CI: 1.36, 1.40; p < .0001). Adults with diabetes, hypertension, asthma, COPD or emphysema or who were women, were more likely to develop BMI≥25 during the pandemic. Women who smoked were more likely to have an increase in BMI than men who smoked during the COVID-19 period.

TriNetX outputs from updated searches undertaken on 24/10/2024 after peer review.

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.

Studies conflict on the significance of burn-induced coagulopathy. We posit that burn-induced coagulopathy is associated with injury severity in burns. Our purpose was to characterize coagulopathy profiles in burns and determine relationships between % total burn surface area (TBSA) burned and coagulopathy using the International Normalized Ratio (INR). Burned patients with INR values were identified in the TriNetX database and analyzed by %TBSA burned. Patients with history of transfusions, chronic hepatic failure, and those on anticoagulant medications were excluded. Interquartile ranges for INR in the burned study population were 1.2 (1.0–1.4). An INR of ≥ 1.5 was used to represent those with burn-induced coagulopathy as it fell outside the 3rd quartile. The population was stratified into subgroups using INR levels

Change from normal BMI category to overweight/obese category, pre-pandemic to May, 2022.

Risk ratios for biological sex on BMI ≥ 25 during the COVID-19 pandemic risk ratio before propensity score matching risk ratio after propensity score matching.

ObjectivesThe treatment landscape for metastatic renal cell carcinoma changed a lot in the last few years. This study aimed to assess the treatment sequences and outcomes for metastatic renal cell carcinoma in a real-world setting.Materials and methodsWe enrolled patients with metastatic renal cell carcinomawho received first-line systemic treatment with tyrosin kinase inhibitors monotherapy, ipilimumab plus nivolumab, or pembrolizumab plus axitinibbetween January2009 and May 2023 on the database of TriNetX network. Overall survival, time on treatment and time to next treatment were evaluated using Kaplan-Meiermethod.ResultsTotally, 4183 received tyrosine kinase inhibitor monotherapy, 1555 received ipilimumab plus nivolumab, and 559 received axitinib plus pembrolizumab. Median time on treatment was 2.5 months for the tyrosine kinase inhibitor monotherapy cohort, 5.4 months for the ipilimumab plus nivolumab cohort, and 8.3 months for the pembrolizumab plus axitinib cohort. Median time to next treatment was 16.6 months for both the tyrosine kinase inhibitor monotherapy and ipilimumab plus nivolumab cohorts, and 22.1 months for the pembrolizumab plus axitinib cohort. Median overall survival was 42.2 months for the tyrosine kinase inhibitor monotherapy cohort, 39.7monthsfor the ipilimumab plus nivolumab cohort, and not reached for the pembrolizumab plus axitinib cohort. In comparison with the tyrosine kinase inhibitor monotherapy cohort, patients in the pembrolizumab plus axitinib cohort showed survival benefit (log-rank p = 0.0168) in overall survival, but not the case in the ipilimumab plus nivolumab cohort.ConclusionThere was a trend toward using first-line immuno-oncology based therapy for patients with metastatic renal cell carcinoma in a real-world practice. Axitinib plus pembrolizumuab cohort had survival benefits over tyrosine kinase inhibitor and ipilimumab plus nivolumab cohorts, while patients in the ipilimumab plus nivolumab cohort had more distant metastases and comorbidities.