Cataract Development Among Pediatric Patients With Uveitis.

Importance: The long-term estimated risk of development of cataracts among pediatric patients with uveitis is not clear. Objective: To describe factors associated with the development of cataracts among pediatric patients with uveitis. Design, Setting, and Participants: This cohort study used the international TriNetX database to enroll pediatric patients with and without uveitis from January 1, 2002, to December 31, 2022. The nonuveitis cohort consisted of randomly selected control patients matched by age, sex, race and ethnicity, and specific comorbidities. Exposure: Diagnosis of uveitis, identified using diagnostic codes. Main Outcomes and Measures: The primary outcome was the risk of developing cataracts among the uveitis group compared with the nonuveitis comparison group, with hazard ratios (HRs) and 95% CIs reported. Results: A total of 22 687 pediatric patients with uveitis (mean [SD] age, 10.3 [5.6] years; 54.2% male) and 22 687 comparators without uveitis (mean [SD] age, 10.3 [5.6] years; 54.5% male) were enrolled in the study. The risk of cataracts was increased among pediatric patients with uveitis up to a follow-up duration of 20 years (HR, 17.17; 95%CI, 12.90-22.80) from the index date. Subgroup analyses revealed an elevated cataract risk across age groups: 0 to 6 years (HR, 19.09; 95% CI, 10.10-36.00), 7 to 12 years (HR, 27.16; 95% CI, 15.59-47.20), and 13 to 18 years (HR, 13.39; 95% CI, 8.84-20.30); both female sex (HR, 13.76; 95% CI, 9.60-19.71) and male sex (HR, 11.97; 95% CI, 8.47-16.91); and Asian (HR, 13.80; 95% CI, 3.28-58.07), Black or African American (HR, 10.41; 95% CI, 5.60-19.36), and White (HR, 15.82; 95% CI, 11.05-22.60) race. Furthermore, increased cataract risks were also observed among those with and without a history of immunosuppressive agents (with: HR, 26.52 [95% CI, 16.75-41.90]; without: HR, 17.69 [95% CI: 11.39-27.40]), a history of steroid eye drop use (with: HR, 29.51 [95% CI, 14.56-59.70]; without: HR, 16.49 [95% CI, 11.92-22.70]), and a history of intraocular procedures (with: HR, 11.07 [95%CI, 4.42-27.71]; without: HR, 14.49 [95% CI, 10.11-20.70]). Conclusions and Relevance: In this cohort study of pediatric patients with uveitis, an elevated risk of cataracts following a uveitis diagnosis was found compared with pediatric patients without uveitis. The findings suggest that pediatric patients with uveitis should be monitored for cataract development.

From psoriasis to psoriatic arthritis: epidemiological insights from a retrospective cohort study of 74,046 patients.

Introduction: To 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. Methods: We 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. Results: PsO 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). Discussion: These 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.

Early clinical response associates with long-term outcomes with ixekizumab in radiographic axial spondyloarthritis.

BACKGROUND: The Assessment of SpondyloArthritis international Society-European Alliance of Associations for Rheumatology recommendations for axial spondyloarthritis (axSpA) management include patient assessment for biological disease-modifying antirheumatic drug (bDMARD) treatment response after at least 12 weeks of treatment. The current treat-to-target strategy for axSpA is to achieve inactive disease (ID; Axial Spondyloarthritis Disease Activity Score (ASDAS) <1.3) or at least low disease activity (LDA; 1.3≤ASDAS<2.1).To investigate the association between treatment response at week 12 and/or week 24 and attainment of the ASDAS<2.1 treat-to-target recommendation at week 52 in bDMARD-naïve patients with radiographic (r-)axSpA treated with ixekizumab (IXE). METHODS: This post hoc analysis included patients randomly assigned to IXE 80 mg every 4 weeks from COAST-V (NCT02696785), a phase 3 trial in bDMARD-naïve patients with r-axSpA. The proportion of patients who achieved ASDAS<2.1 at week 52 was measured among those who attained or not clinically important improvement (CII, ∆ASDAS≥1.1) response, and among those with ID, LDA and high or very high disease activity at week 12 and/or week 24. Non-response was assumed for missing data. RESULTS: Amongst 81 patients, 47 (58.0%) achieved ASDAS CII at week 12, with 70.2% (n=33) achieving ASDAS<2.1 at week 52. At week 24, 52 (64.2%) patients achieved ASDAS CII, with 71.2% (n=37) achieving ASDAS<2.1 at week 52. Of the 24 patients who did not achieve ASDAS CII at either week 12 or week 24, 5 (20.8%) achieved ASDAS<2.1 at week 52. CONCLUSION: This analysis reinforces the current recommendation that continuing treatment in those achieving ASDAS CII at week 12 and/or week 24 increases the likelihood of obtaining ID/LDA at week 52. TRIAL REGISTRATION NUMBER: NCT02696785.

Association of maternal constipation and risk of atopic dermatitis in offspring.

Objectives: Atopic dermatitis (AD) is a chronic and relapsing dermatologic disease that can affect individuals of all ages, including children and adults. The prevalence of AD has increased dramatically over the past few decades. AD may affect children's daily activities, increase their parents' stress, and increase health expenditure. Constipation is a worldwide issue and may affect the gut microbiome. Some research has indicated that constipation might be associated with risk of atopic disease. The primary objective of this retrospective cohort study was to extend and to explore the link between maternal constipation and risk of atopic dermatitis in offspring. Methods: Using the Longitudinal Health Insurance Database, a subset of Taiwan's National Health Insurance Research Database, we identified 138,553 mothers with constipation and 138,553 matched controls between 2005 and 2016. Propensity score analysis was used matching birth year, child's sex, birth weight, gestational weeks, mode of delivery, maternal comorbidities, and antibiotics usage, with a ratio of 1:1. Multiple Cox regression and subgroup analyses were used to estimate the adjusted hazard ratio of child AD. Results: The incidence of childhood AD was 66.17 per 1,000 person-years in constipated mothers. By adjusting child's sex, birth weight, gestational weeks, mode of delivery, maternal comorbidities, and received antibiotics, it was found that in children whose mother had constipation, there was a 1.26-fold risk of AD compared to the children of mothers without constipation (adjusted hazard ratio [aHR]: 1.26; 95% CI, 1.25-1.28). According to subgroup analyses, children in the maternal constipation group had a higher likelihood of AD irrespective of child's sex, birth weight, gestational weeks, mode of delivery, and with or without comorbidities, as well as usage of antibiotics during pregnancy. Compared to the non-constipated mothers, the aHR for the constipated mothers with laxative prescriptions <12 and ≥12 times within one year before the index date were 1.26; 95% CI, 1.24 -1.28 and 1.40; 95% CI, 1.29-1.52, respectively. Conclusion: Maternal constipation was associated with an elevated risk of AD in offspring. Clinicians should be aware of the potential link to atopic dermatitis in the children of constipation in pregnant women and should treat gut patency issues during pregnancy. More study is needed to investigate the mechanisms of maternal constipation and atopic diseases in offspring.

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.

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.

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.

Assessing Uveitis Risk following Pediatric Down Syndrome Diagnosis: A TriNetX Database Study.

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

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.

Association between colchicine use and the risk of dementia among patients with gout: A nationwide retrospective cohort study.

BACKGROUND: Recent findings suggest a link between gout and the development of dementia. Early treatment with colchicine is recommended as a first-line therapy for gout flares. Animal studies demonstrate that colchicine could induce cognitive impairment. This cohort study aimed to investigate the association between colchicine use and the risk of developing dementia. METHODS: In this nationwide cohort study, we performed comparative analysis on 6147 patients ≥40 years, with gout and colchicine new users against 6147 controls to assess subsequent dementia risk. The colchicine group and the control group (urate lowering therapy group) were matched on the bases of age, sex, index year, and comorbidities. All participants were followed for up to 14 years for a diagnosis of dementia considering medical records were retrospectively checked over this period. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Sensitivity analyses were performed to validate our findings. RESULTS: The adjusted hazard ratio (aHR) of dementia for colchicine users was 1.45 (95% CI = 1.05, 1.99) relative to comparison group after adjusting for sex, age, and comorbidities. Sensitivity analysis aiming to minimize underdiagnosed occult dementia at the time of index year yielded consistent positive association. In higher accumulative dose colchicine group (cumulative defined daily dose [cDDD] >30), the aHR of dementia risk for colchicine users was 1.42 (95% CI = 1.03, 1.97) compared with nonusers. For those duration of colchicine use >30 days, the aHR was 1.53 (95% CI = 1.01-2.32) compared to the nonuser group. CONCLUSIONS: A significant risk of dementia was observed in this study in patients with gout using colchicine at higher cDDD and for a longer period. Further research is needed to elucidate the relationship between colchicine, gout, and dementia.

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.

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.