Network of healthcare organizations, together with data partners in Brazil, South Korea, and Japan, to bring clinical facts on more than 250 million patients around the world. Federated model so users of this data are ensured new patients, observations, and results every day, all harmonized to standard terminology like ICD-10 and LOINC without any data wrangling required at the point of care. The raw data is not available to authors of papers and papers in medicine are being retracted.

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

Analysis was performed after propensity score matching for age and gender at the index event.

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 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.

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

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.

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.

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).

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.

IntroductionHuman papillomavirus (HPV) infection has been implicated in autoimmune processes, yet concerns remain about the potential autoimmune risks of HPV vaccination. Juvenile idiopathic arthritis (JIA) is a chronic autoimmune condition that typically manifests in childhood. The relationship between HPV vaccination and the development of JIA remains uncertain.MethodsWe conducted a retrospective cohort study using data from the TriNetX U.S. Collaborative Network. Females aged 9–13 years were included. Three analyses were performed: (1) comparing HPV4-vaccinated vs. unvaccinated matched cohorts; (2) a stricter comparison excluding subjects with positive ANA; (3) comparing single vs. multiple HPV4 doses. Propensity score matching and Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsIn Analysis 1 (n=55,257 pairs) and Analysis 2 (n=53,827 pairs), the HPV4-vaccinated groups showed significantly reduced rates of JIA from 12 to 36 months post-vaccination (HR range: 0.33–0.52). No difference in JIA risk was observed between single and multiple doses in Analysis 3 (n=20,822 pairs). Early-onset JIA (

IntroductionHuman papillomavirus (HPV) infection has been implicated in autoimmune processes, yet concerns remain about the potential autoimmune risks of HPV vaccination. Juvenile idiopathic arthritis (JIA) is a chronic autoimmune condition that typically manifests in childhood. The relationship between HPV vaccination and the development of JIA remains uncertain.MethodsWe conducted a retrospective cohort study using data from the TriNetX U.S. Collaborative Network. Females aged 9–13 years were included. Three analyses were performed: (1) comparing HPV4-vaccinated vs. unvaccinated matched cohorts; (2) a stricter comparison excluding subjects with positive ANA; (3) comparing single vs. multiple HPV4 doses. Propensity score matching and Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsIn Analysis 1 (n=55,257 pairs) and Analysis 2 (n=53,827 pairs), the HPV4-vaccinated groups showed significantly reduced rates of JIA from 12 to 36 months post-vaccination (HR range: 0.33–0.52). No difference in JIA risk was observed between single and multiple doses in Analysis 3 (n=20,822 pairs). Early-onset JIA (

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.

BackgroundPhenome-Wide Association study (PheWAS) is a powerful tool designed to systematically screen clinical observations derived from medical records (phenotypes) for association with a variable of interest. Despite their usefulness, no systematic screening of phenotypes associated with Staphylococcusaureusinfections (SAIs) has been done leaving potential novel risk factors or complications undiscovered.Method and cohortsWe tailored the PheWAS approach into a two-stage screening procedure to identify novel phenotypes correlating with SAIs. The first stage screened for co-occurrence of SAIs with other phenotypes within medical records. In the second stage, significant findings were examined for the correlations between their age of onset with that of SAIs. The PheWAS was implemented using the medical records of 754,401 patients from the Marshfield Clinic Health System. Any novel associations discovered were subsequently validated using datasets from TriNetX and All of Us, encompassing 109,884,571 and 118,538 patients respectively.ResultsForty-one phenotypes met the significance criteria of a p-value < 3.64e-5 and odds ratios of > 5. Out of these, we classified 23 associations either as risk factors or as complications of SAIs. Three novel associations were discovered and classified either as a risk (long-term use of aspirin) or complications (iron deficiency anemia and anemia of chronic disease). All novel associations were replicated in the TriNetX cohort. In the All of Us cohort, anemia of chronic disease was replicated according to our significance criteria.ConclusionsThe PheWAS of SAIs expands our understanding of SAIs interacting phenotypes. Additionally, the novel two-stage PheWAS approach developed in this study can be applied to examine other disease-disease interactions of interest. Due to the possibility of bias inherent in observational data, the findings of this study require further investigation.

This is a retrospective observational cohort study conducted with TriNetx that examines elderly psoriasis patients and the impact of systemic therapies on the incidence of different types of dementia. Our hypotheses were 1. Psoriasis is associated with an increased likelihood of dementia and 2. Treatment with systemic therapies will attenuate the likelihood of developing dementia among patients with psoriasis. We utilized de-identified data from the TriNetX Research Network between 2005-2025. Individuals aged 65-95 without prior history of dementia were included in the analysis. Two primary cohorts were created: 1) psoriasis patients receiving systemic therapies and 2) psoriasis patients managed without systemic therapies and each matched 1:1 to a control group of patients without psoriasis. Primary outcomes were the incidence of Alzheimer’s disease, vascular, and nonvascular dementia assessed over a period of up to 20-years. We identified 4,378,994 patients without psoriasis, 45,713 untreated psoriasis patients, and 14,664 treated psoriasis patients. After meeting index event inclusion criteria and 1:1 PSM, cohorts were matched to their respective non-psoriasis controls (eTable3-8). Over a 20-year follow-up, untreated psoriasis patients were >33% more likely to develop Alzheimer’s (668 vs 474; OR=1.42[1.26-1.60]), vascular (415 vs 313; OR=1.33[1.15-1.54]), and nonvascular dementia (1,985 vs 1,498; OR=1.35[1.26-1.44]) compared to non-psoriasis patients (Table 1). Conversely, treated psoriasis patients were 38% less likely to develop Alzheimer’s (117 vs 189; OR=0.62[0.49-0.78]), 32% less likely to develop vascular dementia (85 vs 124; OR=0.68[0.52-0.90]), and 18% less likely to develop nonvascular dementia (454 vs 554; OR=0.82[0.72-0.93]) compared to non-psoriasis controls (Table 1). In conclusion, Untreated psoriasis is associated with a significantly higher likelihood of dementia compared to non-psoriatic individuals. However, in the presence of systemic therapy for psoriasis, the likelihood of dementia diagnosis is markedly reduced.

ObjectivesTo understand the difference in adverse events (AEs), healthcare resource utilization (HCRU), and kidney failure rates in immunoglobulin A nephropathy (IgAN) patients who initiated systemic glucocorticoid (SGC) treatment compared with those who did not.MethodsThe overall cohort was selected from patients with IgAN (ICD-10 codes N02.8 and N04.1) identified in the TriNetX Dataworks database between January 2011 and May 2022. New initiators of dexamethasone, prednisone, prednisolone, or methylprednisolone (SGC cohort) were propensity score (PS) matched 1:1 with patients who did not receive SGC (non-SGC cohort) based on their characteristics at diagnosis. The index date was the date of SGC initiation; for the non-SGC cohort, a pseudo-index date was assigned using the same lag from diagnosis to index date as their PS-matched pairs. Patients with kidney failure before the index/pseudo-index date and their 1:1 PS-matched pairs were excluded.ResultsThe final analysis was conducted in 802 patients (401 PS-matched pairs, mean age 41.2 years, 55% male). Median duration of follow-up was 3.5 and 3.1 years for the SGC and non-SGC cohorts, respectively. Compared with the non-SGC cohort, patients in the SGC cohort had greater frequency of several AEs, including severe infections, greater annualized HCRU and costs, and greater incidence of kidney failure.ConclusionsThis study found that SGC therapy may increase adverse reactions and HCRU in IgAN patients, while comparatively providing no beneficial effects on preserving kidney function.

De-identified, minimal, aggregated dataset from TriNetX used to plot cumulative incidence of tramadol prescription

There is limited data comparing Azacitidine plus Venetoclax (HMA&Ven) versus traditional intensive chemotherapy with Cytarabine plus Anthracycline (IC) in older patients. We conducted a propensity score-matched cohort study using the TriNetX database to compare the mortality and safety outcomes in this patient population. The analysis resulted in 370 patients in each group. Compared to IC, HMA&Ven had a similar rate of all-cause mortality in 1 year follow-up (HR: 1.16 [95% CI: 0.93-1.44], p-value = 0.186). However, HMA&Ven had fewer neutropenia (HR: 0.72 [95% CI: 0.60-0.87], p-value < 0.001) and sepsis (HR: 0.72 [95% CI: 0.56-0.92], p-value = 0.009). These data suggest that these patients receiving HMA&Ven have fewer adverse events without a difference in survival compared to IC.

Background and objectiveAcute kidney injury (AKI) is a common complication in hospitalized pediatric patients. Previous studies focused on adults found that proteinuria detected during an admission urinalysis is fit to serve as an indicator for AKI and associated clinical outcomes. The objective of this study is to evaluate if proteinuria on the first day of hospital services in hospitalized children is associated with AKI, need for renal replacement therapy, shock and/or antibiotic use, critical care services, and all-cause mortality at 30 days, hypothesizing that it is associated with these outcomes.MethodsThis is a retrospective cohort study using TriNetX electronic health record data of patients 2 to 18 years of age who underwent urinalysis laboratory testing on hospital admission, had three subsequent days of hospital or critical care services billing codes and creatinine laboratory values, and no pre-existing renal-related complex chronic condition. This study evaluated for the frequency, odds, and severity of AKI as defined by Kidney Disease: Improving Global Outcomes modified criteria and assessed for associated clinical outcomes.ResultsThis study included 971 pediatric subjects [435 (44.7%) with proteinuria]. Proteinuria on the first day of hospital services was associated with an increased odds for higher severity AKI on any day of hospitalization (odds ratio [OR] 2.41, CI 1.8–3.23, p