Inverse Probability Of Treatment Weighting Research Articles

GLP-1RA vs DPP-4i Use and Rates of Hyperkalemia and RAS Blockade Discontinuation in Type 2 Diabetes

Hyperkalemia is a common complication in people with type 2 diabetes (T2D) that may limit the use of guideline-recommended renin-angiotensin system inhibitors (RASis). Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs) increase urinary potassium excretion, which may translate into reduced hyperkalemia risk. To compare rates of hyperkalemia and RASi persistence among new users of GLP-1RAs vs dipeptidyl peptidase-4 inhibitors (DPP-4is). This cohort study included all adults with T2D in the region of Stockholm, Sweden, who initiated GLP-1RA or DPP-4i treatment between January 1, 2008, and December 31, 2021. Analyses were conducted between October 1, 2023, and April 29, 2024. GLP-1RAs or DPP-4is. The primary study outcome was time to any hyperkalemia (potassium level >5.0 mEq/L) and moderate to severe (potassium level >5.5 mEq/L) hyperkalemia. Time to discontinuation of RASi use among individuals using RASis at baseline was assessed. Inverse probability of treatment weights served to balance more than 70 identified confounders. Marginal structure models were used to estimate per-protocol hazard ratios (HRs). A total of 33 280 individuals (13 633 using GLP-1RAs and 19 647 using DPP-4is; mean [SD] age, 63.7 [12.6] years; 19 853 [59.7%] male) were included. The median (IQR) time receiving treatment was 3.9 (1.0-10.9) months. Compared with DPP-4i use, GLP-1RA use was associated with a lower rate of any hyperkalemia (HR, 0.61; 95% CI, 0.50-0.76) and moderate to severe (HR, 0.52; 95% CI, 0.28-0.84) hyperkalemia. Of 21 751 participants who were using RASis, 1381 discontinued this therapy. The use of GLP-1RAs vs DPP-4is was associated with a lower rate of RASi discontinuation (HR, 0.89; 95% CI, 0.82-0.97). Results were consistent in intention-to-treat analyses and across strata of age, sex, cardiovascular comorbidity, and baseline kidney function. In this study of patients with T2D managed in routine clinical care, the use of GLP-1RAs was associated with lower rates of hyperkalemia and sustained RASi use compared with DPP-4i use. These findings suggest that GLP-1RA treatment may enable wider use of guideline-recommended medications and contribute to clinical outcomes in this population.

Early postoperative fever as a predictor of pancreatic fistula after pancreaticoduodenectomy: a single-center retrospective observational study

BackgroundThe connection between early postoperative fever and clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy remains unclear. This study aimed to investigate this association and assess the predictive value of early postoperative fever for CR-POPF.MethodsThis retrospective observational study included adult patients who underwent pancreaticoduodenectomy at a tertiary teaching hospital between 2007 and 2019. Patients were categorized into those with early postoperative fever (≥ 38 °C in the first 48 h after surgery) and those without early postoperative fever groups. Weighted logistic regression analysis using stabilized inverse probability of treatment weighting (sIPTW) and multivariable logistic analysis were performed. The c-statistics of the receiver operating characteristic curves were calculated to evaluate the impact on the predictive power of adding early postoperative fever to previously identified predictors of CR-POPF.ResultsOf the 1997 patients analyzed, 909 (45.1%) developed early postoperative fever. The overall incidence of CR-POPF among all the patients was 14.3%, with an incidence of 19.5% in the early postoperative fever group and 9.9% in the group without early postoperative fever. Early postoperative fever was significantly associated with a higher risk of CR-POPF after sIPTW (adjusted odds ratio [OR], 1.73; 95% confidence interval [CI], 1.34–2.22; P < 0.001) and multivariable logistic regression analysis (adjusted OR, 1.88; 95% CI, 1.42–2.49; P < 0.001). The c-statistics for the models with and without early postoperative fever were 0.76 (95% CI, 0.73–0.79) and 0.75 (95% CI, 0.72–0.78), respectively, showing a significant difference between the two (difference, 0.02; 95% CI, 0.00–0.03; DeLong’s test, P = 0.005).ConclusionsEarly postoperative fever is a significant but not highly discriminative predictor of CR-POPF after pancreaticoduodenectomy. However, its widespread occurrence limits its applicability as a predictive marker.

Readmissions Among Patients With Surgically Managed Drug Use Associated-Infective Endocarditis Before and After the Implementation of an Addiction Consult Team: A Retrospective, Observational Analysis.

Patients who undergo cardiac surgery for drug use-associated infective endocarditis (DUA-IE) have high rates of readmissions for recurrent endocarditis, substance use disorder (SUD), and septicemia. Our primary objective was to assess whether exposure to an addiction consult team (ACT) was associated with reduced readmissions in this population. This single-center retrospective analysis identified patients who underwent cardiac surgery for DUA-IE between 1/2012-9/2022 using the Society for Thoracic Surgeons database, and compared the cumulative incidence of readmissions at 1, 3, 6, and 12 months among those cared for before and after the implementation of an ACT in 9/2017, accounting for competing risk of mortality and adjusted for measured confounders using inverse probability of treatment weighting. The 58 patients (35 pre-ACT and 23 post-ACT) were young (36.4 +/- 7.7 years) and predominantly White (53.4%) and male (70.7%). The post-ACT cohort had a significantly lower risk of readmission at 1 month (adjusted risk difference [RD] -23.8% [95% CI -94.4%, -8.3%], P = 0.005) and 3 months (RD -34.1% [-55.1%, -13.1%], P = 0.005), but not at 6 or 12 months. In a sensitivity analysis, the post-ACT cohort also had significantly lower risk of readmissions for SUD complications at 3 months. ACT exposure was associated with a lower risk of short-term readmission among patients with surgically managed DUA-IE, possibly due to a reduction in SUD-related complications. Additional studies are needed to replicate these findings and to identify ways to sustain the potential benefits of ACTs over the longer term.

Insulin resistance and periodontitis: Mediation by blood pressure.

This study investigated the association between the triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, and moderate/severe periodontitis and the role of blood pressure as a mediator in this association. A second aim was to assess the role of cardiometabolic conditions such as obesity, hypertension, and dyslipidemia as potential effect modifiers. Data from 5733 US adults aged 30-64 years and with complete periodontal examination were analyzed (NHANES 2011-2014). Participants were classified as having moderate/severe periodontitis or mild/no periodontitis according to the CDC/AAP criteria as the outcome. The exposure was the TyG index, while both systolic (SBP), and diastolic (DBP) blood pressure were tested as mediators using parametric g-formula. Analyses were adjusted for relevant confounders, namely, age, sex, ethnicity, poverty-income ratio, and smoking, using inverse probability treatment weighting. Obesity status (based on a body mass index ≥30 kg/m2), self-report of hypertension and dyslipidemia (calculated based on the thresholds provided by National Cholesterol Education Program-Adult Treatment Panel-III) were tested as effect modifiers. The findings showed the TyG index to be associated with increased odds of moderate/severe periodontitis [odds ratio (OR), 95% confidence interval (CI) = 1.17 (1.11-1.23)], with 50% of the total effect mediated by SBP. Stratified analysis showed a stronger association in individuals with obesity, hypertension, and dyslipidemia compared to those without these conditions. However, in those taking anti-hypertensive medications, the association was partially mitigated. Sensitivity analysis using imputed data showed consistent results. The TyG index was associated with increased odds of moderate/severe periodontitis, especially in individuals with obesity, hypertension, and dyslipidemia. SBP levels partially mediated this association.

Effect of bile duct resection on the prognosis of patients with hepatocellular carcinoma combined with extrahepatic bile duct tumor thrombus

BackgroundSurgical therapy is the most optimal treatment for hepatocellular carcinoma (HCC) combined with bile duct tumor thrombus (BDTT) patients. However, whether to perform bile duct resection (BDR) is still controversial. The purpose of this multicenter research is to compare the effect of BDR on the prognosis of extrahepatic BDTT patients.MethodsWe collected the data of 111 HCC patients combined with extrahepatic BDTT who underwent radical hepatectomy from June 1, 2004 to December 31, 2021. Those patients had either received hepatectomy with extrahepatic bile duct resection (BDR group) or hepatectomy without bile duct resection (NBDR group). Inverse probability of treatment weighting (IPTW) was used to reduce the potential bias between two groups and balance the influence of confounding factors in baseline data. Then compare the prognosis between the two groups of patients. Cox regression model was used for univariate and multivariate analysis to further determine the independent risk factors that influence the prognosis of HCC-BDTT patients.ResultsThere were 38 patients in the BDR group and 73 patients in the NBDR group. Before and after IPTW, there were no statistical significance in OS, RFS and intraoperative median blood loss between the two groups (all P > 0.05). Before IPTW, the median postoperative hospital stay in the NBDR group was shorter (P = 0.046) and the grade of postoperative complications was lower than BDR group (P = 0.014). After IPTW, there was no difference in postoperative hospital stay between the two groups (P > 0.05). The complication grade in the NBDR group was still lower than that in the BDR group (P = 0.046). The univariate analysis showed that TNM stage and portal vein tumor thrombus (PVTT) were significantly correlated with OS (both P < 0.05). Preoperative AFP level, TNM stage and prognostic nutritional index (PNI) were significantly correlated with postoperative RFS (all P < 0.05). Multivariate analysis showed that tumor TNM stage was an independent risk factor for the OS rate (P = 0.014). TNM stage, PNI and AFP were independent predictors of RFS after radical hepatectomy (all P < 0.05).ConclusionsFor HCC-BDTT patients, hepatocellular carcinoma resection combined with choledochotomy to remove the tumor thrombus may benefit more.

The Association of Adverse Pregnancy Outcomes With Overactive Bladder Anticholinergics.

The pregnancy safety and teratogenicity of overactive bladder (OAB) anticholinergic medications in humans are unknown. The aim of this study was to determine if the use of OAB anticholinergics during pregnancy was associated with adverse pregnancy outcomes or congenital malformation. Using routinely collected health care data from Ontario, Canada, we conducted a retrospective cohort study and identified women aged 18-45 years who gave birth between 2004 and 2022 and were eligible for provincial drug benefits. We used gestational age and birth dates to approximate conception dates. The primary exposure was filling a prescription for an OAB anticholinergic during pregnancy (compared with nonusers). The coprimary outcomes were pregnancy complication (which included preterm birth or low birth weight) and congenital malformation. Poisson regression models with generalized estimating equations and inverse probability of treatment weighting were used to estimate risk ratios (RRs). We identified 138,271 births, of which 479 (0.3%) had exposure to an OAB anticholinergic, for a median of 60 (interquartile range, 30-120) days. The most common OAB anticholinergic was oxybutynin (84%). In the weighted cohort, the risk of a pregnancy complication was significantly elevated (RR, 1.65; 95% confidence interval [CI], 1.40-1.95; P < 0.01; absolute risk difference + 9.9% [95% CI, +5.9, +13.9]), with a dose-response relationship close to statistical significance (P = 0.07). The risk of congenital malformations with OAB anticholinergic use was not significant (RR, 1.24; 95% CI, 0.85-1.80; P = 0.26). Pregnant women who take OAB anticholinergic medications have a higher risk of pregnancy complications, but not congenital malformations, compared with non-OAB anticholinergic users. This information can be used when counseling women of child-bearing age about these medications.

Comparative effectiveness of vancomycin and metronidazole on event-free survival after initial infection in patients with Clostridioides difficile—a German multicentre cohort study

ObjectivesThe objective of this study is to examine the comparative effectiveness of vancomycin and metronidazole in a confirmatory analysis of event-free survival (EFS) after initial infection in patients with Clostridioides difficile from a German multicentre cohort study. MethodsThe IBIS multicentre cohort enrolled patients with an index episode of C. difficile infection between August 2017 and September 2020. The primary endpoint was EFS, defined as response to treatment with metronidazole or vancomycin within 10 days of initiation, absence of recurrence and death from any cause up to 90 days post-treatment. A Cox proportional hazards model with inverse probability of treatment weighting was used to investigate the comparative effectiveness of this outcome. Additionally, subgroup analyses were performed based on severe and non-severe infections. ResultsOf the 489 patients included, 118 (24%) received initial treatment with metronidazole and 371 (76%) with vancomycin. Of these, 78/118 (66.1%) and 247/371 (66.6%), respectively, responded to treatment within 10 days, neither developed a recurrence nor died within 90 days and thus achieved the outcome of EFS. In the subgroup of non-severe infections, 74/293 patients (25.3%) received metronidazole, and 219/293 (74.7%) received vancomycin. Of these, 33/74 (44.6%) metronidazole patients and 150/219 (68.5%) vancomycin patients survived event free. The Cox proportional hazards model revealed differences in EFS for the overall population and both subgroups (reference metronidazole: all severity levels: hazard ratio [HR] 0.46, [95% CI, 0.33–0.65]; non-severe: HR 0.39; [95% CI, 0.24–0.60]; severe: HR 0.52; [95% CI, 0.28–0.95]). DiscussionOur analysis confirms current changes in guidelines, as it supports the superiority of vancomycin compared with metronidazole across all severity levels.

Association of a novel restrictive housing diversion program with rates of mental health and self-injury in prison.

Restrictive housing for control purposes (RHCP, a form of solitary confinement) is used in prisons in response to disruptive behaviors, including violence. North Carolina prisons introduced the rehabilitative diversion unit (RDU) in 2016 as an alternative to and step-down from RHCP. We compared rates of psychiatric treatment and self-injury among men enrolled in the RDU and men eligible for the RDU but placed in RHCP. We used Poisson regression to calculate rate ratios (RRs) and 95% confidence intervals (CIs) for these outcomes, using inverse probability of treatment weights to adjust for confounders. The cohort included 1,225 men in the RDU group and 3,059 in the RHCP group. In RHCP, the adjusted psychiatric treatment rate was 2.6 times (95% CI: 1.8, 3.8) and the adjusted self-injury incident rate was 1.2 times (95% CI: 0.6, 2.8) that in RDU. Nearly all self-injury incidents in RDU occurred during "non-participating time" (i.e., in a restrictive housing setting and not actively participating in RDU). After excluding non-participating time from the RDU group's person time, the adjusted RR for self-injury incidents was 23.5 (95% CI: 8.6, 64.2). These results further knowledge of potential benefits of diversion from restrictive housing. Continued development, implementation, and evaluation is needed.

Hypnotic Use and the Risk of Cardiovascular Diseases in Insomnia Patients.

We aimed to examine the association between hypnotic agents and cardiovascular outcomes in general individuals with insomnia. In a propensity score matched cohort of UK Biobank (UKB) participants with insomnia, Cox proportional hazard model was used to estimate the association between regular use of hypnotic agents and predetermined cardiovascular outcomes including incident coronary heart diseases (CHD), heart failure (HF), stroke, and cardiovascular death. Inverse probability of treatment weighting, competing risk models, and shared frailty models were further performed during sensitivity analysis. Drug-target Mendelian randomization (MR) analyses were employed for further evaluation of the association between therapeutic targets of hypnotics and cardiovascular diseases. During a median follow-up of 14.3 years, the matched cohort documented a total of 929 CHD cases, 360 HF cases, 262 stroke cases, and 180 cardiovascular deaths. No significant association was detected between Z-meds and CHD, stroke, and cardiovascular mortality. Benzodiazepine use was significantly associated with the increased risk of CHD, HF, and cardiovascular mortality. The inverse probability of treatment weighting, competing risk models, and shared frailty models didn't alter the above associations. Moreover, drug-target MR analyses corroborated the safety of Z-meds in the general population regarding cardiovascular health. Our findings suggested the heterogeneous associations between different categories of hypnotics and incident cardiovascular events in individuals with insomnia. Both observational and genetic evidence raised safety concerns regarding the cardiovascular impact of benzodiazepines. No cardiovascular hazard of Z-meds was discovered in the UKB population with insomnia.

Predictive value of the early postoperative hemoglobin-to-red blood cell distribution width ratio for acute kidney injury in elderly intertrochanteric fracture patients

BackgroundHemoglobin-to-red blood cell distribution width ratio (HRR) had great predictive value for the prognosis of malignant tumors and cardiovascular disease. However, its predictive value for the occurrence of acute kidney injury (AKI) in elderly intertrochanteric fracture patients remains unclear. This study aims to analyze the correlation between the early postoperative HRR and the risk of postoperative AKI in elderly intertrochanteric fracture patients.MethodsWe reviewed the medical records of 307 elderly intertrochanteric fracture patients in this single-center retrospective cohort study. We performed univariate analysis on the relevant parameters, and parameters with significant differences were included in the following logistic regression model for multivariate analysis. Then, we used a receiver operating characteristic (ROC) curve to evaluate the predictive value of the early postoperative HRR level for AKI in elderly intertrochanteric fracture patients. Patients were divided into a high HRR group and a low HRR group according to the cutoff point determined by ROC curve analysis. Subsequently, the relevance between postoperative HRR and AKI was further determined using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW).ResultsThe area under the curve of the early postoperative HRR for predicting postoperative AKI was 0.714 (95% CI: 0.618–0.809). The cutoff value was 5.44. The sensitivity was 72.7%, and the specificity was 70.8%. Patients were divided into low HRR (⩽ 5.44) and high HRR (> 5.44) groups according to the cutoff value. PSM and IPTW analysis indicated that the risk of AKI in the low HRR group was significantly higher than that in the high HRR group in both the matched cohort (OR = 6.914, 95% CI: 1.714–46.603, p = 0.016) and the weighted group (OR = 2.784, 95% CI: 1.415–5.811, p = 0.040).ConclusionsEarly postoperative HRR is an accurate, accessible, and economical blood test parameter that can predict the risk of postoperative AKI in elderly patients with femoral intertrochanteric fracture.

Association of glucagon-like peptide-1 receptor agonists with suicidal ideation and self-injury in individuals with diabetes and obesity: a propensity-weighted, population-based cohort study.

Regulators worldwide are reviewing safety data on glucagon-like peptide-1 receptor agonists (GLP-1RA), following reports by the Icelandic Medicines Agency in July 2023 of suicidal ideation and self-injury (SIS) in individuals taking liraglutide and semaglutide. We aimed to assess the risk of SIS in new users of GLP-1RA when compared with sodium-glucose cotransporter 2 inhibitors (SGLT-2i) users, prescribed to treat type 2 diabetes in individuals with obesity. This is a cohort study combining several population-wide databases and covering a Spanish population of five million inhabitants, including all adults with obesity who initiated treatment with either GLP-1RA or SGLT-2i for type 2 diabetes from 2015 to 2021. To estimate the comparative effect of GLP-1RA on the risk of SIS, we employed a new user, active comparator design and we carried out multivariable Cox regression modelling with inverse probability of treatment weighting (IPTW) based on propensity scores. We performed several stratified and sensitivity analyses. We included 3040 patients initiating treatment with GLP-1RA and 11,627 with SGLT-2i. When compared with patients treated with SGLT-2i, those in the GLP-1RA group were younger (55 vs 60 years old, p<0.001), had more anxiety (49.4% vs 41.5%, p<0.001), sleep disorders (43.2% vs 34.1%, p<0.001) and depression (24.4% vs 19.0%, p<0.001), and were more obese (35.1% of individuals with BMI ≥40 vs 15.1%, p<0.001). After propensity score weighting, standardised mean differences between groups were <0.1 for all covariates, showing adequate balance between groups at baseline after adjustment. In the main per-protocol analyses we found no evidence that GLP-1RA increased the incidence of SIS (HR 1.04; 95% CI 0.35, 3.14). Intention-to-treat analyses resulted in an HR of 1.36 (95% CI 0.51, 3.61). In analyses excluding individuals with no BMI information and using imputation for BMI missing values, respective HRs were 0.89 (95% CI 0.26, 3.14) and 1.29 (95% CI 0.42, 3.92). Stratified analyses showed no differences between subgroups. Our findings do not support an increased risk of SIS when taking GLP-1RA in individuals with type 2 diabetes and obesity; however, the rarity of SIS events and the wide uncertainty of effect size (although null, effect may be compatible with a risk as high as threefold) calls for a cautious interpretation of our results. Further studies, including final evaluations from regulatory bodies, are called for to discard a causal link between GLP-1RA and suicidality.

The use of glucocorticoid in severe fever with thrombocytopenia syndrome: a retrospective cohort study.

Severe fever with thrombocytopenia syndrome (SFTS) is prevalent in East Asia. However, the use of glucocorticoids (GCs) in the treatment of SFTS remains controversial. In this retrospective cohort study, we collected the data from patients with SFTS at Wuhan Union Hospital to evaluate the effect of GC therapy. Mortality and secondary infections were compared as outcomes. After searching public databases, we also included articles that examined GC use in patients with SFTS for meta-analysis. Patients treated with GC had higher fatality rates (21.1% vs. 11.9%, respectively; P=0.006) and a longer length of stay (10.6 ± 5.1 vs. 9.5 ± 4.2, respectively; P=0.033). In cohorts adjusted using propensity score matching and inverse probability of treatment weighting, no significant differences in fatality rates and length of stay were observed. A meta-analysis of 4243 SFTS patient revealed that those treated with GCs had significantly higher mortality (OR=3.46, 95% CI =2.12-5.64, P<0.00001) and secondary infection rate (OR=1.97, 95% CI=1.45-2.67, P<0.0001). GC should be used cautiously when treating SFTS. No significant differences were identified in terms of mortality and secondary infection rates between patients with SFTS treated with or without GC.

Comparative Safety and Effectiveness of Ustekinumab and Anti-TNF in Elderly Crohn's Disease Patients.

Biologic therapies are associated with increased infection risk among elderly patients with inflammatory bowel disease (IBD). However, there are few data on the safety and effectiveness of ustekinumab compared with anti-tumor necrosis factor (anti-TNF) agents in the elderly. The study sought to compare the safety and effectiveness of ustekinumab and anti-TNF agents in elderly Crohn's disease (CD) patients. Patients ≥60 years of age who commenced ustekinumab or an anti-TNF agent for CD were included in this retrospective multicenter cohort. The primary outcome was incidence of serious infections requiring hospitalization. Effectiveness was assessed by clinical remission, clinical response, and treatment persistence rates at 6 months. We adjusted for confounders using inverse probability of treatment weighting (IPTW) and performed a logistic regression analysis to assess factors associated with serious infections, clinical remission, and treatment persistence. Eighty-three patients commencing ustekinumab and 124 commencing anti-TNF therapy were included. There was no difference in serious infection rates between anti-TNF agents (2.8%) and ustekinumab (3.1%) (P = .924) after propensity adjustment. Clinical remission rates were comparable at 6 months for ustekinumab (55.9%) and anti-TNF agents (52.4%) (P = .762). There was a significant reduction in HBI at 6 months in both groups. Treatment persistence was comparable between ustekinumab (90.6%) and anti-TNF agents (90.0%) at 6 months. Cox regression analysis did not show differences in treatment persistence (hazard ratio, 1.23; 95% confidence interval, 0.57-2.61; P = .594) and serious infection incidence (hazard ratio, 1.38; 95% confidence interval, 0.25-7.57; P = .709) by 6 months. We observed comparable safety and effectiveness for ustekinumab and anti-TNF agents in treating elderly CD patients.

Impact of Physical Activity on Overall Survival and Liver Cirrhosis Incidence in Steatotic Liver Disease: Insights from a Large Cohort Study Using Inverse Probability of Treatment Weighting.

Physical activity is a cornerstone of a healthy lifestyle, with benefits in managing chronic diseases. This study investigates the relationship between physical activity and liver-related outcomes with or without steatotic liver diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD and increased alcohol intake (MetALD). The primary outcomes of interest were overall survival in the entire population, individuals without steatotic liver disease, patients with MASLD, and those with MetALD. The secondary outcomes included the incidence of liver cirrhosis. Participants were categorized based on physical activity frequency and Kaplan-Meier survival curves and Cox proportional hazards models were used for analysis. Higher physical activity was associated with significantly better survival in the overall cohort and MASLD cohort before and after inverse probability of treatment weighting (IPTW). In participants without steatotic liver disease and the MetALD cohort, higher physical activity showed significant survival improvement after IPTW. For the incidence of liver cirrhosis, higher physical activity showed significant associations before IPTW in the overall cohort and MASLD cohort, but these associations were not significant after IPTW. Marginal significance was observed in the MetALD cohort before and after IPTW. In conclusion. promoting physical activity may be key in improving liver-related outcomes.

Mall Cop or Robocop? The Political Determinants of Police Militarization in Brazil

Police militarization is prevalent worldwide. Despite growing interest in the consequences of militarization, few studies focus on its causes. Through the case of Brazilian municipal police forces, we explore the connection between partisan ideology and police militarization. Some research shows that leftist administrations in democracies are more likely to emphasize human rights and less likely to militarize the police. However, leftist administrations might militarize police forces more than centrist and right-wing parties to compensate for perceptions of lower competence to deal with security issues, especially when they face high levels of violent crime. Using inverse probability of treatment weights, we show an association between leftist mayors and higher militarization of municipal police forces. Furthermore, in contexts of high homicide rates, mayors of Brazil’s leading leftist party, the Workers' Party, tend to militarize local police more than others.

Real-World Outcomes in Patients with Advanced/Metastatic Renal Cell Carcinoma Receiving Cabozantinib or Other Tyrosine Kinase Inhibitors After Checkpoint Inhibitor-Based Therapy

BACKGROUND: Checkpoint inhibitor (CPI)-based therapy is recommended for first-line treatment of advanced/metastatic renal cell carcinoma (mRCC). Cabozantinib is a tyrosine kinase inhibitor (TKI) approved in the USA for treating mRCC, including after CPI-based therapy. However, data on the benefits of subsequent TKI therapy are limited. OBJECTIVE: To study the real-world use and outcomes of cabozantinib versus other TKIs after CPI-based therapy for mRCC. METHODS: This retrospective study used data from the US Oncology Network electronic health record database supplemented by chart review. Patients initiated TKI therapy between 2016 and 2021 after CPI-based therapy. The primary endpoint was real-world response rate in the first 6 months of treatment (RR-6m; physician assessment). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Covariates were adjusted by inverse probability of treatment weighting. RESULTS: Of 485 included patients, 331 received cabozantinib and 154 another TKI. Baseline characteristics were generally similar between arms. For cabozantinib versus other TKIs, adjusted RR-6m (available for 69.3% of patients) was 62.5% versus 46.0% (rate difference: superiority, 16.5% [95% CI: 7.8–25.1], p = 0.0002), adjusted ORR was 62.4% versus 49.4% (p = 0.0020), adjusted median OS was 19.2 versus 19.1 months (p = 0.7353) and adjusted median PFS was 7.9 versus 9.2 months (p = 0.8752). CONCLUSIONS: Cabozantinib following CPI-based therapy was effective for treating mRCC in the US real-world setting. Differences in adjusted RR-6m and ORR significantly favored cabozantinib versus other TKIs. The lack of OS difference may reflect differences in post-index therapy.

Comparative effectiveness of dupilumab and omalizumab on asthma exacerbations and systemic corticosteroid prescriptions: Real-world US ADVANTAGE study

In the United States, dupilumab is approved for moderate-to-severe eosinophilic or oral corticosteroid-dependent asthma, and omalizumab is approved for managing moderate-to-severe allergic asthma uncontrolled by inhaled corticosteroids. However, limited comparative effectiveness data exist for these biologics due to differing patient characteristics and treatment histories. This study assessed the real-world effectiveness of dupilumab and omalizumab for asthma in patients in the United States. In this retrospective observational study, TriNetX Dataworks electronic medical record data were used to identify patients with asthma age ≥12 years who initiated (index) dupilumab or omalizumab between November 2018 and September 2020 and who had at least 12 months of pre- and post-index clinical information. Inverse probability of treatment weighting was applied to balance potential confounding in treatment groups. Asthma exacerbation rates and systemic corticosteroid (SCS) prescriptions were compared using a doubly robust negative binomial regression model, adjusting for baseline exacerbation/SCS rates and patient characteristics with ≥10% standardized differences after inverse probability of treatment weighting. All inclusion and exclusion criteria were met by 2138 dupilumab patients and 1313 omalizumab patients. After weighting, the majority of baseline characteristics were balanced (standard difference <10%) between the 2 groups. Dupilumab was associated with a 44% lower asthma exacerbation rate (P< .0001) versus omalizumab. Additionally, dupilumab treatment significantly (P< .05) reduced SCS prescriptions by 28% during the follow-up period compared with omalizumab treatment. The US ADVANTAGE real-world study demonstrated a significant reduction in severe asthma exacerbations and SCS prescriptions for patients prescribed dupilumab compared with patients prescribed omalizumab during 12 months of follow-up.

Periodontitis and Diabetes Complications: A Danish Population-Based Study

Conflicting evidence suggests a link between diabetes-related microvascular complications and periodontitis. Reliable estimates have been hindered by small sample sizes and residual confounding. Moreover, the combined effects of microvascular complications and dyslipidemia on periodontitis have not been explored. Therefore, this study aimed to investigate the association between individual and combined diabetic microvascular complications (i.e., neuropathy and retinopathy) and moderate/severe periodontitis in a Danish population-based study. In addition, we assessed whether dyslipidemia modified these associations. This study comprised 15,922 participants with type 2 diabetes from the Health in Central Denmark study. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for individual and joint microvascular diabetes complications. The models adjusted for potential confounders, including sociodemographic factors, lifestyle behaviors, and health conditions. Inverse probability of treatment weighting (IPTW) balanced measured confounders between periodontitis and nonperiodontitis participants. Sensitivity analyses tested the findings’ robustness by estimating E-values for unmeasured confounding and varying microvascular complication definitions. After IPTW, adjusted models revealed that diabetic neuropathy (OR 1.36, 95% CI 1.14 to 1.63) and retinopathy (OR 1.21, 95% CI 1.03 to 1.43) were significantly associated with moderate/severe periodontitis. Moreover, the coexistence of microvascular complications increased the odds 1.5-fold for moderate/severe periodontitis (OR 1.51, 95% CI 1.23 to 1.85). An effect modification of dyslipidemia on an additive scale was found, indicated by a positive relative excess risk due to interaction of 0.24 for neuropathy, 0.11 for retinopathy, and 0.44 for both complications. Sensitivity analysis ruled out unmeasured confounders and microvascular complication definitions as explanatory factors. Diabetic neuropathy and retinopathy, individually and combined, were associated with moderate/severe periodontitis. In addition, dyslipidemia had an additive positive effect modification on diabetic microvascular complications, elevating the odds of moderate/severe periodontitis. These findings may aid in identifying at-risk subgroups for diabetes-related microvascular complications and periodontitis, optimizing efforts to mitigate disease burden.

Health care resource utilization and costs for treatment-experienced people with HIV switching or restarting antiretroviral regimens since 2018.

There is a need to understand health care resource utilization (HCRU) and costs associated with treatment-experienced people with HIV (PWH) switching treatment regimens. To describe HCRU and cost during lines of antiretroviral therapy (ART) for treatment-experienced PWH switching to or restarting guideline-recommended, integrase strand transfer inhibitor (INSTI)-based multitablet regimens and single-tablet regimens. This retrospective claims study used data from Optum Research Database (January 1, 2010, to March 31, 2020) to identify lines of therapy (LOTs) for treatment-experienced adults who switched to or restarted INSTI-based regimens between January 1, 2018, and December 31, 2019. The first LOT during the study period was included in the analysis. We examined all-cause HCRU and costs and HIV-related HCRU and combined costs to the health plan and direct patient costs by site of service and compared between INSTI-based regimens: bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (single tablet) vs dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) (single tablet), dolutegravir + emtricitabine/tenofovir alafenamide (DTG+FTC/TAF) (multitablet), and dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG+FTC/TDF) (multitablet). Analysis of HCRU by site of service was conducted following inverse probability treatment weighting. Multivariable regression was conducted using a generalized linear model with stepwise covariate selection to estimate HIV-related medical costs and control for remaining differences after inverse probability treatment weighting. 4,251 PWH were identified: B/F/TAF (n = 2,727; 64.2%), DTG/ABC/3TC (n = 898; 21.1%), DTG+FTC/TAF (n = 539; 12.7%), and DTG+FTC/TDF (n = 87; 2.1%). PWH treated with DTG+FTC/TAF had a significantly higher mean of all-cause ambulatory visits than PWH treated with B/F/TAF (1.8 vs 1.6, P < 0.001). A significantly smaller proportion of PWH treated with DTG/ABC/3TC had an all-cause ambulatory visit vs PWH treated with B/F/TAF (90.6% vs 93.9%, P < 0.001). All-cause total costs were not significantly different between regimens. Mean (SD) medical HIV-related costs per month during the LOT were not significantly different between B/F/TAF $699 (3,602), DTG/ABC/3TC $770 (3,469), DTG+FTC/TAF $817 (3,128), and DTG+FTC/TDF $3,570 (17,691). After further controlling for unbalanced measures, HIV-related medical costs during the LOT were higher (20%) but did not reach statistical significance for DTG/ABC/3TC (cost ratio = 1.20, 95% CI = 0.851-1.694; P = 0.299), 49% higher for DTG+FTC/TAF (cost ratio = 1.489, 95% CI = 1.018-2.179; P = 0.040), and almost 11 times greater for DTG+FTC/TDF (cost ratio = 10.759, 95% CI = 2.182-53.048; P = 0.004) compared with B/F/TAF. HIV-related medical costs during the LOT were lowest for PWH treated with INSTI-based single-tablet regimens. Simplifying treatment regimens may help PWH maintain lower health care costs.

Statin Therapy, Inflammation, and Outcomes in Patients Hospitalized for COVID-19: A Prospective Multicenter Cohort Study

BackgroundStatins are lipid-lowering agents with anti-inflammatory effects. Data surrounding the benefits of statins in patients with coronavirus disease 2019 (COVID-19) are conflicting. We sought to better understand the impact of statins in the context of COVID-19-related inflammation. MethodsWe leveraged the International Study of Inflammation in COVID-19, a prospective multicenter cohort of patients hospitalized for COVID-19 between February 2020 and October 2022. Participants underwent systematic assessment of biomarkers of inflammation. We used logistic regression modeling and inverse probability-of-treatment weighting (IPTW) to examine the association between prior statin use and the composite outcome of in-hospital death, need for mechanical ventilation, and need for renal replacement therapy. ResultsA total of 4464 patients were included in the study, of whom 1364 (27.5%) were taking a statin prior to admission. There were 1061 primary outcome events, including 540 deaths, 854 mechanical ventilation and 313 renal replacement therapy. Amongst biomarkers of inflammation, statin use was associated solely with lower levels of soluble urokinase plasminogen activator receptor (suPAR) after adjusting for known confounders. In multivariable logistic regression analysis, statin use was associated with lower odds of the composite outcome (adjusted odds ratio (aOR) 0.63, 95% CI [0.53-0.76]) compared to patients not on statins. Findings were consistent with IPTW (aOR 0.92, 95% CI [0.89- 0.95]). The proportion of the effect of statin on the primary outcome mediated by suPAR was estimated at 31.5%. ConclusionPrior-statin use is associated with improved outcomes and lower inflammation as measured by suPAR levels in patients hospitalized for COVID-19.