Low serum testosterone is associated with an increased risk of first-time renal calculi in men without testosterone replacement therapy.

The incidence of low serum testosterone has been increasing in men of all ages across a period which also corresponds to an increasing prevalence of kidney stones. Currently, the relationship between testosterone and kidney stones is unclear. Using the TriNetX Research Network, we performed a retrospective cohort study to evaluate the risk of developing an initial kidney stone in men based on their total testosterone level. Men aged ≥18 were divided into a low testosterone (<300 ng/dL) and normal testosterone (≥ 300 ng/dL) cohort. Men were excluded if they had a history of a kidney stone encounter diagnosis before testosterone measurement and a history of testosterone therapy prescription at any point. Propensity score matching was employed with an absolute standardized mean difference of less than 0.1 used as an indicator of successful matching. Our main outcome of interest was risk of developing an initial kidney stone in men aged ≥18 and within age-based subgroups. In men 18 and older, low testosterone was associated with a higher risk of one or more kidney stone encounter diagnoses (HR 1.12, 95% CI [1.09-1.15]). When stratified by age, no significant association between low testosterone and kidney stone encounter diagnoses was seen in men aged 18-24 (HR 1.09, 95% CI [0.85-1.39]). The highest risk was observed in men with low testosterone aged 34-44 (HR 1.29, 95% CI [1.17-1.38]). In this study, low serum testosterone was associated with an increased risk of initial kidney stone diagnosis in adult men without testosterone therapy prescriptions at any point in their life. Stratifying by age, the increased risk appears to begin in men aged 25, with the highest observed risk in men aged 33-44.

Suicidal ideation following ketamine prescription in patients with recurrent major depressive disorder: a nation-wide cohort study.

Ketamine has gained attention for its effective treatment for patients with major depressive disorder (MDD) and suicidal ideation; Despite numerous studies presenting the rapid efficacy, long-term benefit in real-world populations remains poorly characterized. This is a retrospective cohort study using TriNetX US Collaborative Network, a platform aggregating electronic health records (EHRs) data from 108 million patients from 62 health care organizations in the US, and the study population includes 514,988 patients with a diagnosis of recurrent MDD who were prescribed relevant treatment in their EHRs. The prescription of ketamine was associated with significantly decreased risk of suicidal ideation compared to the prescription of other common antidepressants: HR = 0.63 (95% CI: 0.53-0.76) at 1 day - 7 days, 0.67 (95% CI: 0.59-0.77) at 1 day - 30 days, 0.69 (95% CI: 0.62-0.77) at 1 day - 90 days, 0.74 (95% CI: 0.67-0.81) at 1 day - 180 days, and 0.78 (95% CI: 0.69-0.83) at 1 day - 270 days. This trend was especially robust among adults over 24 years of age, females, males, and White patients with recurrent MDD. This study provides real-world evidence that ketamine has long-term benefits in mitigating suicidal ideation in patients with recurrent MDD. Future work should focus on optimizing dosage regimens for ketamine, understanding the mechanism, and the difference in various demographic subpopulations.

Co-prevalence of chronic rhinosinusitis and inflammatory bowel disease: A large aggregated electronic health record study.

KEY POINTS: IBD patients have a 4.04-fold elevated likelihood of having CRS compared to non-IBD patients. CRS patients have a 4.23-fold elevated likelihood of having IBD compared to non-CRS patients. The risk of CRS development after IBD is five times higher than IBD development after CRS.

Association of Semaglutide With Tobacco Use Disorder in Patients With Type 2 Diabetes : Target Trial Emulation Using Real-World Data.

BACKGROUND: Reports of reduced desire to smoke in patients treated with semaglutide, a glucagon-like peptide receptor agonist (GLP-1RA) medication for type 2 diabetes mellitus (T2DM) and obesity, have raised interest about its potential benefit for tobacco use disorders (TUDs). OBJECTIVE: To examine the association of semaglutide with TUD-related health care measures in patients with comorbid T2DM and TUD. DESIGN: Emulation target trial based on a nationwide population-based database of patient electronic health records. SETTING: United States, 1 December 2017 to 31 March 2023. PARTICIPANTS: Seven target trials were emulated among eligible patients with comorbid T2DM and TUD by comparing the new use of semaglutide versus 7 other antidiabetes medications (insulins, metformin, dipeptidyl-peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors, sulfonylureas, thiazolidinediones, and other GLP-1RAs). MEASUREMENTS: The TUD-related health care measures (medical encounter for diagnosis of TUD, smoking cessation medication prescriptions, and smoking cessation counseling) that occurred within a 12-month follow-up were examined using Cox proportional hazards and Kaplan-Meier survival analyses. RESULTS: The study compared 222 942 new users of antidiabetes medications including 5967 of semaglutide. Semaglutide was associated with a significantly lower risk for medical encounters for TUD diagnosis compared with other antidiabetes medications, and was strongest compared with insulins (hazard ratio [HR], 0.68 [95% CI, 0.63 to 0.74]) and weakest but statistically significant compared with other GLP-1RAs (HR, 0.88 [CI, 0.81 to 0.96]). Semaglutide was associated with reduced smoking cessation medication prescriptions and counseling. Similar findings were observed in patients with and without a diagnosis of obesity. For most of the group comparisons, the differences occurred within 30 days of prescription initiation. LIMITATION: Documentation bias, residual confounding, missing data on current smoking behavior, body mass index, and medication adherence. CONCLUSION: Semaglutide was associated with lower risks for TUD-related health care measures in patients with comorbid T2DM and TUD compared with other antidiabetes medications including other GLP-1Ras, primarily within 30 days of prescription. These findings suggest the need for clinical trials to evaluate semaglutide's potential for TUD treatment. PRIMARY FUNDING SOURCE: National Institutes of Health.

Non-Insulin Antidiabetic Agents and Lung Cancer Risk in Drug-Naive Patients with Type 2 Diabetes Mellitus: A Nationwide Retrospective Cohort Study.

Lung cancer (LC) is the second most common cancer and the leading cause of cancer deaths in the U.S. Insulin therapy, a key treatment for managing Type 2 Diabetes Mellitus (T2DM), is associated with increased LC risk. The impact of non-insulin antidiabetic drugs, particularly GLP-1 receptor agonists (GLP-1RAs), on LC risk is not well understood. This study evaluated LC risk in T2DM patients, comparing seven non-insulin antidiabetic agents to insulin. Using the TriNetX Analytics platform, we analyzed the de-identified electronic health records of 1,040,341 T2DM patients treated between 2005 and 2019, excluding those with prior antidiabetic use or LC diagnoses. We calculated hazard ratios and confidence intervals for LC risk and used propensity score matching to control for confounding factors. All non-insulin antidiabetic drugs, except alpha-glucosidase inhibitors, were associated with significantly reduced LC risk compared to insulin, with GLP-1RAs showing the greatest reduction (HR: 0.49, 95% CI: 0.41, 0.59). GLP-1RAs were consistently associated with lowered LC risk across all histological types, races, genders, and smoking statuses. These findings suggest that non-insulin antidiabetic drugs, particularly GLP-1RAs, may be preferable for managing T2DM while reducing LC risk.

Association of adverse cardiovascular events with gabapentin and pregabalin among patients with fibromyalgia.

OBJECTIVE: Fibromyalgia, a chronic pain disorder, impacts approximately 2% of adults in the US. Gabapentin and pregabalin are common treatments to manage fibromyalgia-related pain. Our recent study showed the risk of adverse cardiovascular events increased in diabetic neuropathy patients who were prescribed gabapentin or pregabalin. Here, we investigated whether the prescription of gabapentin or pregabalin has similar cardiovascular risk in patients with fibromyalgia. METHODS: This retrospective cohort study leveraged electronic health records from 64 US healthcare organizations with 112 million patients. The study population included 105,602 patients first diagnosed with fibromyalgia and followed by a prescription of gabapentin, pregabalin, or other FDA-approved drugs for treating fibromyalgia from 2010 to 2019. Outcomes were deep venous thrombosis (DVT), myocardial infarcts (MI), peripheral vascular disease (PVD), strokes, heart failure, and pulmonary embolism (PE). In propensity-score-matched cohorts, 1-year and 5-year hazard ratios (HRs) were computed with their respective 95% confidence intervals (CIs). Additionally, we conducted sensitivity analyses on the subpopulations without other possible indications. RESULTS: For 5-year follow-up, gabapentin increased the risk of PVD (HR = 1.46, 95% CI = 1.17-1.80), MI (HR = 1.31, 95% CI = 1.03-1.66), heart failure (HR = 1.27, 95% CI = 1.10-1.48), DVT (HR = 1.80, 95% CI = 1.33-2.44), and PE (HR = 2.23, 95% CI = 1.62-3.07). Pregabalin increased the risk of DVT (HR = 1.49, 95% CI = 1.01-2.20), and PE (HR = 2.24, 95% CI = 1.43-3.50). For 1-year follow-up, gabapentin increased the risk of PVD (HR = 1.32, 95% CI = 1.11-1.57), DVT (HR = 1.35, 95% CI = 1.09-1.68), and PE (HR = 1.36, 95% CI = 1.17-1.57). Pregabalin increased the risk of PVD (HR = 1.32, 95% CI = 1.06-1.63) and PE (HR = 1.25, 95% CI = 1.03-1.52). Sensitivity analyses showed similar trends. CONCLUSION: In fibromyalgia patients, the prescription of gabapentin and pregabalin moderately increased the risk of several adverse cardiovascular events. This risk, together with benefits and other adverse reactions, should be considered when prescribing these medications for fibromyalgia patients.

Glucagon-Like Peptide 1 Receptor Agonists and 13 Obesity-Associated Cancers in Patients With Type 2 Diabetes.

Importance: Thirteen human malignant neoplasms have been identified as obesity-associated cancers (OACs), ie, the presence of excess body fat is associated with increased risk of developing cancer and worse prognosis in patients with these specific tumors. The glucagon-like peptide receptor agonist (GLP-1RA) class of pharmaceuticals are effective agents for the treatment of type 2 diabetes (T2D) and for achieving weight loss, but the association of GLP-1RAs with the incident risk of 13 OACs is unclear. Objective: To compare the incident risk of each of the 13 OACs in patients with T2D who were prescribed GLP-1RAs vs insulins or metformin. Design, Setting, and Participants: This retrospective cohort study was based on a nationwide multicenter database of electronic health records (EHRs) of 113 million US patients. The study population included 1 651 452 patients with T2D who had no prior diagnosis of OACs and were prescribed GLP-1RAs, insulins, or metformin during March 2005 to November 2018. Data analysis was conducted on April 26, 2024. Exposures: Prescription of GLP-1RAs, insulins, or metformin. Main Outcomes and Measures: Incident (first-time) diagnosis of each of the 13 OACs occurring during a 15-year follow-up after the exposure was examined using Cox proportional hazard and Kaplan-Meier survival analyses with censoring applied. Hazard ratios (HRs), cumulative incidences, and 95% CIs were calculated. All models were adjusted for confounders at baseline by propensity-score matching baseline covariates. Results: In the study population of 1 651 452 patients with T2D (mean [SD] age, 59.8 [15.1] years; 827 873 [50.1%] male and 775 687 [47.0%] female participants; 5780 [0.4%] American Indian or Alaska Native, 65 893 [4.0%] Asian, 281 242 [17.0%] Black, 13 707 [0.8%] Native Hawaiian or Other Pacific Islander, and 1 000 780 [60.6%] White participants), GLP-1RAs compared with insulin were associated with a significant risk reduction in 10 of 13 OACs, including in gallbladder cancer (HR, 0.35; 95% CI, 0.15-0.83), meningioma (HR, 0.37; 95% CI, 0.18-0.74), pancreatic cancer (HR, 0.41; 95% CI, 0.33-0.50), hepatocellular carcinoma (HR, 0.47; 95% CI, 0.36-0.61), ovarian cancer (HR, 0.52; 95% CI, 0.03-0.74), colorectal cancer (HR, 0.54; 95% CI, 0.46-0.64), multiple myeloma (HR, 0.59; 95% CI, 0.44-0.77), esophageal cancer (HR, 0.60; 95% CI, 0.42-0.86), endometrial cancer (HR, 0.74; 95% CI, 0.60-0.91), and kidney cancer (HR, 0.76; 95% CI, 0.64-0.91). Although not statistically significant, the HR for stomach cancer was less than 1 among patients who took GLP-1RAs compared with those who took insulin (HR, 0.73; 95% CI, 0.51-1.03). GLP-1RAs were not associated with a reduced risk of postmenopausal breast cancer or thyroid cancer. Of those cancers that showed a decreased risk among patients taking GLP-1RAs compared with those taking insulin, HRs for patients taking GLP-1RAs vs those taking metformin for colorectal and gallbladder cancer were less than 1, but the risk reduction was not statistically significant. Compared with metformin, GLP-1RAs were not associated with a decreased risk of any cancers, but were associated with an increased risk of kidney cancer (HR, 1.54; 95% CI, 1.27-1.87). Conclusions and Relevance: In this study, GLP-1RAs were associated with lower risks of specific types of OACs compared with insulins or metformin in patients with T2D. These findings provide preliminary evidence of the potential benefit of GLP-1RAs for cancer prevention in high-risk populations and support further preclinical and clinical studies for the prevention of certain OACs.

The association of COVID-19 with increased pediatric ventriculoatrial shunt failures: a national retrospective cohort.

OBJECTIVE: During the COVID-19 pandemic, the authors' institution managed ventriculoatrial (VA) shunt complications in 2 teenage patients in close proximity to a symptomatic COVID-19 infection. Systemic thrombotic events are an established complication of COVID-19 infection due to a hypercoagulable state. Thrombotic complications, particularly elevated central venous pressure, can cause VA shunt failure. The true effect of COVID-19 on patients with intravascular devices is currently unknown. In this study, the authors aimed to determine if there was an association between COVID-19 infection and VA shunt failure. METHODS: TriNetX, an aggregated electronic health record platform, was used to analyze data of more than 13 million US pediatric patients. Two matched cohorts of patients < 18 years of age with a VA shunt were defined. Group 1 (n = 311) had a positive laboratory test for COVID-19 from March 1, 2020, to March 31, 2022. Group 2 (n = 311), a control group, had any medical appointment from March 1, 2020, to March 31, 2022, and never had a positive laboratory test for COVID-19. The authors analyzed outcomes 1 year after testing positive for COVID-19 in group 1, and after the medical appointment in group 2. Outcomes included shunt complications, shunt revisions or replacements, and thromboembolic complications. To protect patient privacy, individual results of fewer than 10 patients are not specified in TriNetX. RESULTS: Group 1 had a greater odds of mechanical shunt complication than group 2 (20% vs 4%, OR 5.71, 95% CI 3.07-10.62). Group 1 had a greater odds of shunt reoperation than group 2 (11% vs < 3%, OR > 3.7, 95% CI 1.72-7.62). There were 1-10 patients in group 1 (≤ 3% of group 1) who experienced a thromboembolism due to the shunt, compared with no patients in group 2 who had a thromboembolism due to the shunt. CONCLUSIONS: This analysis demonstrates an association of shunt complications, reoperations, and thromboembolic events in patients with VA shunts following COVID-19 infection.

Five-Year Incidence of Progression to Osteoarthritis and Total Joint Arthroplasty in Patients Prescribed Glucagon-Like Peptide 1 Receptor Agonists.

BACKGROUND: Research has suggested that glucagon-like peptide-1 receptor agonists (GLP-1-RAs) may have therapeutic effects on osteoarthritis of the hip and knee, in addition to managing diabetes and obesity. However, there is a lack of understanding regarding the association between GLP-1-RA use and the diagnosis of osteoarthritis (OA) of the hip and knee. METHODS: A collaborative network analytics platform was queried for obese diabetic (n = 1,094,198), obese nondiabetic (n = 916,235), and nonobese diabetic (n = 157,305) patients who had an index visit between 2015 and 2017. Patients who had pre-existing hip and/or knee OA were excluded. A 1:1 propensity score matching was used to balance GLP-1-RA use in stratified cohorts for age, sex, race, body mass index, and hemoglobin A1c. The primary outcomes were rates of progression to hip OA, knee OA, major joint injections, total hip arthroplasty, and total knee arthroplasty. Cox proportional hazards models determined hazard ratios (HRs) between cohorts prescribed and not prescribed GLP-1-RAs. RESULTS: All patients had a five-year follow-up. Rates of progression to hip and knee OA were higher among the GLP-1-RA users in both obese diabetic (hip HR: 1.63, 95% confidence interval [CI]: 1.46 to 1.82; knee HR: 1.52, CI: 1.41 to 1.64) and nonobese diabetic (hip HR: 1.78, CI: 1.50 to 2.10; knee HR: 1.58, CI: 1.39 to 1.80) cohorts. These diabetic cohorts received higher rates of major joint injections, though there was no difference in rates of total hip arthroplasty or total knee arthroplasty. No differences in five-year outcomes were seen when comparing obese, nondiabetic patients who were prescribed GLP-1-RAs with obese, nondiabetic patients not exposed to GLP-1-RAs. CONCLUSIONS: This five-year analysis found a greater risk of progression to hip and knee OA among obese and non-obese diabetic GLP-1-RA users. Further studies should explore GLP-1-RA effects upon glucose management, weight loss, and lower extremity arthritis development. LEVEL OF EVIDENCE: III, retrospective cohort study.

Epidemiological Trends and Outcomes of Unicompartmental Knee Arthroplasty Among 104 Million Patients in the United States.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) is an alternative to total knee arthroplasty (TKA) for localized osteoarthritis. Recent advancements in UKA implant design and expanding patient criteria may have increased its utilization. However, few studies have examined the use of UKA in the United States. Thus, this study assessed the current and projected future trends of UKA and robotic UKA in the United States through 2035, along with postoperative outcomes. METHODS: A collaborative healthcare research network was queried to identify patients who had undergone UKA. Primary outcomes measured included prevalence (P), incidence proportion (IP), and incidence rate (IR) from 2012 to 2022. Chi-squared analyses were done to compare outcomes across categorical data. Regression modeling was performed to project UKA to the year 2035. Statistical significance was held at P < .05 for all analyses. RESULTS: In 2022, 1,662 UKAs were performed within the network, a 590% increase from 2012 (241 performed). The IP increased on an average annual basis by 41.8%, the IR by 50%, and the P by 51.3%. A year following UKA, conversion to TKA was the most common orthopaedic complication (39.9%). As of 2022, there were 68 robotic UKAs performed, a 518% increase from the 11 performed in 2012. Regression analysis for UKA through 2035 showed that IP will be 0.04%, IR will be 1.75 × 10-6 cases/person-day, and P will be 0.3%. CONCLUSIONS: These findings are consistent with prior studies indicating a higher utilization of UKA over the past decade. Reported complications were not uncommon, as nearly 40% of patients required a conversion to a TKA. Further research is needed to optimally identify criteria for appropriate patients and determine the benefits robotic UKA may provide, specifically reducing the risk of conversion to a TKA.

Low-Dose Aspirin Is the Safest Prophylaxis for Prevention of Venous Thromboembolism After Total Knee Arthroplasty Across All Patient Risk Profiles.

BACKGROUND: The International Consensus Meeting on Venous Thromboembolism (ICM-VTE) in 2022 proclaimed low-dose aspirin as the most effective agent in patients across all risk profiles undergoing joint arthroplasty. However, data on large patient populations assessing trends in chemoprophylactic choices and related outcomes following total knee arthroplasty (TKA) remain scant. The present study was designed to characterize the clinical use of various chemoprophylactic agents in patients undergoing TKA and to determine the efficacy of aspirin compared with other agents in patient groups stratified by VTE risk profiles. METHODS: This study utilized a national database to determine the proportion of patients undergoing TKA who received low-dose aspirin versus other chemoprophylaxis between 2012 and 2022. VTE risk profiles were determined on the basis of comorbidities established in the ICM-VTE. The odds ratios (ORs) and 95% confidence intervals (CIs) between various classes of thromboprophylaxis in patients with high and low risk of VTE were calculated. The odds of deep-vein thrombosis (DVT), pulmonary embolus (PE), bleeding events, infections, mortality, and hospitalizations were also assessed in the 90-day postoperative period for propensity-matched cohorts receiving low-dose (81 mg) aspirin only versus other prophylaxis, segregating patients by VTE risk profile. RESULTS: A total of 126,692 patients undergoing TKA across 60 health-care organizations were included. The proportion of patients receiving low-dose aspirin increased from 7.65% to 55.29% between 2012 and 2022, whereas the proportion of patients receiving other chemoprophylaxis decreased from 96.25% to 42.98%. Low-dose-aspirin-only use increased to approximately 50% in both high-risk and low-risk populations but was more likely in low-risk populations (OR, 1.17; 95% CI, 1.15 to 1.20) relative to high-risk populations. Both low-risk and high-risk patients in the low-dose-aspirin-only cohorts had decreased odds of DVT, PE, bleeding, infections, and hospitalizations compared with other prophylaxis regimens. CONCLUSIONS: The findings of the present study on a very large population of patients undergoing TKA support the recent ICM-VTE statement by showing that low-dose aspirin is a safe and effective method of prophylaxis in patients across various risk profiles. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Association of GLP-1 Receptor Agonists and Hepatocellular Carcinoma Incidence and Hepatic Decompensation in Patients With Type 2 Diabetes.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a leading cause of cancer death. HCC is preventable with about 70% of HCC attributable to modifiable risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), Food and Drug Administration-approved medications for treating type 2 diabetes mellitus (T2DM), have pleiotropic effects on counteracting risk factors for HCC. Here we evaluate the association of GLP-1RAs with incident HCC risk in a real-world population. METHODS: This retrospective cohort included 1,890,020 patients with a diagnosis of T2DM who were prescribed GLP-1RAs or other non-GLP-1RA anti-diabetes medications and had no prior diagnosis of HCC. Incident (first-time) diagnosis of HCC and hepatic decompensating events during a 5-year follow-up was compared between cohorts of patients prescribed GLP-1 RAs vs other anti-diabetes medications. Time-to-first-event analysis was performed using Kaplan-Meier survival analysis with hazard ratio and 95% confidence interval calculated. RESULTS: GLP-1RAs were associated with a lower risk of incident HCC with hazard ratio of 0.20 [0.14-0.31], 0.39 [0.21-0.69], 0.63 [0.26-1.50] compared with insulin, sulfonylureas, and metformin, respectively. GLP-1RAs were associated with a significantly lower risk of hepatic decompensation compared with 6 other anti-diabetes medications. Reduced risks were observed in patients without and with different stages of fatty liver diseases, with more profound effects in patients without liver diseases. Similar findings were observed in patients with and without obesity and alcohol or tobacco use disorders. GLP-1RA combination therapies were associated with decreased risk for HCC and hepatic decompensations compared with monotherapies. CONCLUSIONS: GLP-1RAs were associated with a reduced risk of incident HCC and hepatic decompensation compared with other anti-diabetes medications in patients with T2DM. These findings provide supporting evidence for future studies to investigate the underlying mechanisms and their clinical use.

Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population.

Alcohol use disorders are among the top causes of the global burden of disease, yet therapeutic interventions are limited. Reduced desire to drink in patients treated with semaglutide has raised interest regarding its potential therapeutic benefits for alcohol use disorders. In this retrospective cohort study of electronic health records of 83,825 patients with obesity, we show that semaglutide compared with other anti-obesity medications is associated with a 50%-56% lower risk for both the incidence and recurrence of alcohol use disorder for a 12-month follow-up period. Consistent reductions were seen for patients stratified by gender, age group, race and in patients with and without type 2 diabetes. Similar findings are replicated in the study population with 598,803 patients with type 2 diabetes. These findings provide evidence of the potential benefit of semaglutide in AUD in real-world populations and call for further randomized clinicl trials.

Association between abductor tears and hip pathology: A nationwide large cohort study.

Introduction: Although gluteal tears have been observed in a substantial percentage of total hip arthroplasty (THA) patients and hip osteoarthritis (OA) has been shown to alter the function of the gluteal muscles, the association between gluteal tears and hip OA has not been characterized. Therefore, we evaluated (1) the overlap between hip OA and gluteal tears, (2) the relative risks of gluteal tears in patients who have hip OA, and (3) gluteal tear-free survival after diagnosis or treatment for hip osteoarthritis. Methods: This retrospective study sourced data from TriNetX, a research network that aggregates data from over 92 million patients. Relative risks for gluteal tears were calculated for known risk factors for gluteal tears, age ≥45 years, female sex, and obesity, as well as for hip OA, hip injections, and THA. A subgroup analysis was performed utilizing a Cox proportional hazard model for patients who were diagnosed with hip OA, received a hip injection, or underwent THA in 2015 to assess gluteal tear-free survival over a 9-year timeframe. Results: There was a large degree of overlap between patients with hip OA and gluteal tears, as 17.9% of patients with hip OA and 27.5% of patients with a gluteal tear also had the other pathology. Hip OA was associated with a markedly increased risk of a gluteal tear compared to healthy controls (Relative risk: 26.75, 95% CI: 26.64-26.86). Upon controlling for the established risk factors of gluteal tears, patients with hip OA had a markedly more likely to subsequently be diagnosed with an abductor tear (Hazard ratio: 12.46, 95% CI: 11.75-13.22). Conclusion: Overall, these findings suggest a strong association between hip OA and the development of gluteal tears, in which further investigation is merited to determine the biomechanical pathophysiology underlying this potential relationship to inform prevention and treatment strategies.

Obesity is Associated with Increased Risk of New-Onset Chronic Rhinosinusitis: A United States Population-Based Cohort Study.

OBJECTIVE: The aim of this study was to determine the risk of a new-encounter diagnosis of unspecified chronic rhinosinusitis (CRS), CRS with nasal polyps (CRSwNP), and eosinophilic granulomatosis with polyangiitis (EGPA) 1 and 2 years following body mass index (BMI) classification of obesity utilizing a large-population-based analytics platform. STUDY DESIGN: Retrospective cohort analysis SETTING: The U.S. Collaborative Network within the TriNetX Analytics platform contains deidentified electronic health record (EHR) data of more than 100 million patients and was used to determine the association between obesity and a new encounter diagnosis of 3 CRS phenotypes in this study. RESULTS: After 1:1 propensity score matching, patients with an overweight BMI and obesity were at a higher risk for a new-encounter diagnosis of unspecified CRS and CRSwNP compared to healthy-weight individuals. The obesity cohort had the greatest increased risk of new-onset unspecified CRS with a relative risk of 1.23 (95% CI: 1.20-1.25) and 1.26 (95% CI: 1.24-1.28) 1 and 2 years following BMI classification, respectively. CONCLUSION: Our study indicates an association between obesity and new-onset unspecified CRS and CRSwNP. With the increasing prevalence of obesity in the United States population, it will be important to understand how obesity-associated CRS may affect treatment response. Future prospective studies are needed to assess causality and define a mechanistic link.

Association of semaglutide with reduced incidence and relapse of cannabis use disorder in real-world populations: a retrospective cohort study.

Cannabis is the most frequently used illicit drug in the United States with more than 45 million users of whom one-third suffer from a cannabis use disorder (CUD). Despite its high prevalence, there are currently no FDA-approved medications for CUD. Patients treated with semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) approved for treating type 2 diabetes (T2D) and for weight management have reported reduced desire to drink and smoke. Preclinical studies have shown that semaglutide decreased nicotine and alcohol consumption. Preclinical and preliminary clinical evidence of semaglutide's potential beneficial effects on various substance use disorders led us to evaluate if it pertained to CUD. In this retrospective cohort study of electronic health records (EHRs) from the TriNetX Analytics Network, a global federated health research network of approximately 105.3 million patients from 61 large healthcare organizations in the US, we aimed to assess the associations of semaglutide with both incident and recurrent CUD diagnosis compared to non-GLP-1RA anti-obesity or anti-diabetes medications. Hazard ratio (HR) and 95% confidence intervals (CI) of incident and recurrent CUD were calculated for 12-month follow-up by comparing propensity-score matched patient cohorts. The study population included 85,223 patients with obesity who were prescribed semaglutide or non-GLP-1RA anti-obesity medications, with the findings replicated in 596,045 patients with T2D. In patients with obesity (mean age 51.3 years, 65.6% women), semaglutide compared with non-GLP-1RA anti-obesity medications was associated with lower risk for incident CUD in patients with no prior history CUD (HR: 0.56, 95% CI: 0.42-0.75), and recurrent CUD diagnosis in patients with a prior history CUD (HR: 0.62, 95% CI: 0.46-0.84). Consistent reductions were seen for patients stratified by gender, age group, race and in patients with and without T2D. Similar findings were replicated in the study population with T2D when comparing semaglutide with non-GLP-1RA anti-diabetes medications for incident CUD (HR: 0.40, 95% CI: 0.29-0.56) and recurrent CUD (HR: 0.66, 95% CI: 0.42-1.03). While these findings provide preliminary evidence of the potential benefit of semaglutide in CUD in real-world populations, further preclinical studies are warranted to understand the underlying mechanism and randomized clinical trials are needed to support its use clinically for CUD.

The Association between Hormone Replacement Therapy and Gastroparesis in Post-Menopausal Women: A Worldwide Database Analysis.

Female sex hormones have been hypothesized to influence the higher prevalence of gastroparesis in females. This study investigated the effects of hormone replacement therapy (HRT) on gastroparesis and its related symptoms, medication use, and diagnostic testing in post-menopausal women. Utilizing the TriNetX platform, we conducted a population-based cohort study involving post-menopausal women aged 50 or older, with and without HRT. One-to-one propensity score matching was performed to adjust for age, race, ethnicity, diabetes, body mass index (BMI), and hemoglobin A1c. The exclusion criteria included functional dyspepsia, cyclic vomiting syndrome, and surgical procedures. After applying the exclusion criteria, we identified 78,192 post-menopausal women prescribed HRT and 1,604,822 not prescribed HRT. Post-propensity matching, each cohort comprised 67,874 patients. A total of 210 of the post-menopausal women prescribed HRT developed an ICD encounter diagnosis of gastroparesis at least 30 days after being prescribed HRT compared to post-menopausal women not prescribed HRT (OR = 1.23, 95% CI [1.01-1.51] p-value = 0.0395). These associations persisted in sensitivity analysis over 5 years (OR = 1.65, 95% CI [1.13-2.41] p-value = 0.0086). HRT was associated with increased GI symptoms, including early satiety (OR = 1.22, 95% CI [1.03-1.45] p-value = 0.0187), domperidone use (OR = 2.40, 95% CI [1.14-5.02] p-value = 0.0163), and undergoing gastric emptying studies (OR = 1.67, 95% CI [1.39-2.01] p-value < 0.0001). HRT is linked to an increased risk of developing an ICD encounter diagnosis of gastroparesis.

Does rickets carry an increased risk of osteomyelitis and septic arthritis? An aggregated electronic health record data study.

To investigate the prevalence of osteomyelitis and septic arthritis in pediatric patients with rickets, compared to the general population. A retrospective cohort study was conducted using the TriNetX analytics network, which aggregates deidentified electronic health record data from over 105 million US patients. We queried pediatric patients with rickets, based on ICD-10-CM (International Classification of Diseases, Tenth Revision, Clinical Modification) encounter diagnoses. Patients with any ICD-10-CM encounter diagnoses of osteomyelitis or septic arthritis were reported. We established a control cohort of pediatric patients without rickets. Of 7337 pediatric patients (≤18 years old) with a rickets diagnosis, 96 [1.31%, 95% confidence interval (CI): 1.05%-1.57%] had a diagnosis of osteomyelitis and 28 (0.38%, 95% CI: 0.24%-0.52%) had a diagnosis of septic arthritis. In comparison, of the 17 240 604 pediatric patients without a rickets diagnosis, 16 995 (0.10%, 95% CI: 0.10%-0.10%) had a diagnosis of osteomyelitis and 8521 (0.05%, 95% CI: 0.05%-0.05%) had a diagnosis of septic arthritis. The relative risk for an osteomyelitis diagnosis in pediatric patients with a rickets diagnosis was 13.27 (95% CI: 10.86-16.23), while the relative risk for a septic arthritis diagnosis was 7.72 (95% CI: 5.33-11.18). Pediatric patients with a diagnosis of rickets have over 10- and 5-times higher relative risks for having a diagnosis of osteomyelitis and septic arthritis, respectively, compared to those without a diagnosis of rickets. This is the first study to explore musculoskeletal infections in rickets patients, highlighting the importance of clinicians being vigilant about these conditions.