1,720,976 research outputs found
The Effects of Drug-Drug Interactions Between Direct-Acting Oral Anticoagulants and Antiseizure Medications: A Target Trial Emulation
Full text linkAll direct oral anticoagulants (DOAC) and some antiseizure medications (ASM) interact with cytochrome P450 3A4 (CYP3A4) or P-glycoprotein (P-gp). Concomitant use of these medications may cause drug-drug interactions that increase the risk for thromboembolism. Existing studies assessing this association are conflicting, limited by small sample size, or are conducted on non-US populations.
This new-user, retrospective cohort study emulates a target trial using Merative MarketScan insurance claims data from 2011 to 2019. We included US adults currently using a DOAC who initiated treatment with an ASM that interacts with CYP3A4 or P-gp or an ASM that does not interact with CYP3A4 or P-gp. We excluded persons who were not continuously insured for a year prior to the start of follow-up or who had history of concomitant DOAC and ASM use. We evaluated time-to-event for thromboembolism as well as the incidence rate in this taking interacting and non-interacting drug combinations. We calculated inverse probability of treatment weights using baseline age, sex, comorbidities, and comedications. We used these in a weighted Cox regression to compute an adjusted hazards ratio.
Among the 33,117 participants included in the study, 5,388 (16%) initiated an interacting drug combination and 27,729 (84%) initiated a non-interacting drug combination. The incidence of thromboembolism per 100 person-years was 2.01 (95% CI: 0.51, 8.01) in the interacting group and 0.88 (95% CI: 0.11, 7.11) in the non-interacting group. After weighting, we found that those taking an interacting combination had 1.46 (95% CI: 0.85, 2.51) times the hazard for a thromboembolic event compared to those taking a non-interacting combination.
Among US adults, concomitantly using a DOAC with an antiseizure medication that interacts with P-gp and CYP3A4 appeared to increase the risk for thromboembolism, but the effect did not achieve statistical significance, possibly due to the limited event count. Additional studies collecting more events are needed to confirm the results of this study
The Effects of Drug-Drug Interactions Between Direct-Acting Oral Anticoagulants and Antiseizure Medications: A Target Trial Emulation
Full text linkAll direct oral anticoagulants (DOAC) and some antiseizure medications (ASM) interact with cytochrome P450 3A4 (CYP3A4) or P-glycoprotein (P-gp). Concomitant use of these medications may cause drug-drug interactions that increase the risk for thromboembolism. Existing studies assessing this association are conflicting, limited by small sample size, or are conducted on non-US populations.
This new-user, retrospective cohort study emulates a target trial using Merative MarketScan insurance claims data from 2011 to 2019. We included US adults currently using a DOAC who initiated treatment with an ASM that interacts with CYP3A4 or P-gp or an ASM that does not interact with CYP3A4 or P-gp. We excluded persons who were not continuously insured for a year prior to the start of follow-up or who had history of concomitant DOAC and ASM use. We evaluated time-to-event for thromboembolism as well as the incidence rate in this taking interacting and non-interacting drug combinations. We calculated inverse probability of treatment weights using baseline age, sex, comorbidities, and comedications. We used these in a weighted Cox regression to compute an adjusted hazards ratio.
Among the 33,117 participants included in the study, 5,388 (16%) initiated an interacting drug combination and 27,729 (84%) initiated a non-interacting drug combination. The incidence of thromboembolism per 100 person-years was 2.01 (95% CI: 0.51, 8.01) in the interacting group and 0.88 (95% CI: 0.11, 7.11) in the non-interacting group. After weighting, we found that those taking an interacting combination had 1.46 (95% CI: 0.85, 2.51) times the hazard for a thromboembolic event compared to those taking a non-interacting combination.
Among US adults, concomitantly using a DOAC with an antiseizure medication that interacts with P-gp and CYP3A4 appeared to increase the risk for thromboembolism, but the effect did not achieve statistical significance, possibly due to the limited event count. Additional studies collecting more events are needed to confirm the results of this study
DEVELOPMENT AND VALIDATION OF A MODERN PRESCRIPTION-BASED RISK SCORE TO PREDICT HEALTHCARE SPENDING
No full textPrescription-drug based risk scores offer an important alternative to diagnosis-based risk scoring systems when diagnostic information is unavailable; however, their value depends upon a given score’s ability to capture the current therapeutic landscape. We performed a retrospective cohort study using Merative MarketScan administrative claims data from continuously enrolled, commercially insured adults between January 2021 and December 2022 to develop and validate a modern, prescription-based risk score for predicting healthcare expenditures. Prescription use was described using over 300 binary drug categories, and total healthcare spending was the primary outcome. We characterized the cohort with descriptive statistics and fit several machine learning models that vary in their approaches to regularization and decision-making, including elastic net regression, random forest, and extreme gradient boosting, using 60% of the sample for model development and 40% for validation. Predictor weights were assigned based on beta coefficients from the elastic net regression model, with expenditures modeled on a logarithmic scale. The drug-only risk score achieved an R2 of 0.135 in the validation dataset, improving to 0.173 with the addition of age and sex. These results are comparable to many existing prescription-based risk scores predicting future total healthcare expenditures. Our findings underscore the potential of updated prescription-based risk scores for expenditure prediction and support further research to optimize model performance
HETEROGENEITY OF TREATMENT EFFECTS OF GLUCAGON-LIKE PEPTIDE-1 (GLP-1) RECEPTOR AGONISTS ON WEIGHT LOSS: A RETROSPECTIVE COHORT STUDY
Full text linkBackground: While there is high quality evidence supporting the effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1) for the treatment of obesity, less is known regarding how such effectiveness may vary across different patient subpopulations.
Objectives: To quantify heterogeneity in weight loss response among GLP-1 users, stratified by patient age, sex, race/ethnicity, diabetes, and baseline body mass index (BMI).
Methods: We used TriNetX, a database containing electronic health records from 81 academic medical centers in the United States, to identify adults with at least 6-month continuous GLP-1 use between September 2014 and November 2023. Our primary outcome was percentage change in BMI from baseline, defined as the most recent BMI measurement within 6 months prior to GLP-1 initiation, overall and across different subpopulations of interest. We used linear mixed-effects models with natural splines to examine BMI changes over time, adjusting for individuals’ demographics and clinical characteristics.
Results: Among 23,291 GLP-1 users, the mean baseline BMI was 37.3 ± 7.7 kg/m² and 65.2% were female. During the 6-month follow-up period, 42% achieved ≥5% BMI reduction. There was no statistically significant reduction in BMI between older (≥65 years) and younger adults (-4.1% vs. -4.7%, p=0.132). There were modest, though statistically significant, differences in BMI reduction by sex (females: -5.1% vs males: -3.5%, p<0.001) and race (Black: -4.1% vs White: -4.8%, p<0.001). Individuals with no diabetes experienced substantially greater weight loss than patients with diabetes (-6.7% vs -3.5%, p<0.001). Compared to patients with baseline BMI<30 (-2.0%), patients with BMI 30-35 showed greater reduction (-4.5%, p<0.001), and those with BMI≥35 showed the largest reduction (-5.2%, p<0.001).
Conclusions: Among this large, diverse cohort of adults in the United States, real-world effectiveness of GLP-1 was greater among women, Whites, individuals without diabetes, and those with higher baseline BMI. These findings can be used to inform further research as well as treatment selection among those who may be eligible for pharmacologic treatment of obesity
USE OF GLUCAGON-LIKE PEPTIDE 1 AGONISTS (GLP-1s) AMONG INDIVIDUALS UNDERGOING BARIATRIC SURGERY IN THE UNITED STATES: A RETROSPECTIVE COHORT STUDY
Full text linkImportance: Although randomized and well-controlled observational studies demonstrate the efficacy of glucagon-like peptide 1 agonists (GLP-1s) for weight management after bariatric surgery, little is known regarding the frequency and predictors of such use.
Objective: To characterize the use and factors associated with GLP-1 initiation among U.S. adults undergoing bariatric surgery.
Design: Retrospective cohort study.
Setting: National multicenter database of electronic health records of ~113 million U.S. adults.
Participants: Adults undergoing bariatric surgery from 2015 to 2021 who did not use GLP-1s during the 12-months prior to surgery.
Exposures: Sociodemographic (age, sex, race, region, etc) and clinical (bariatric surgery procedures, body mass index [BMI], comorbidities, co-medications) factors.
Measurements: We first used descriptive statistics to characterize GLP-1 initiation after bariatric surgery. We then used Cox proportional hazards models to identify baseline patient characteristics associated with GLP-1 initiation. We also used time-dependent Cox models to examine the association of post-surgery BMI with GLP-1 initiation.
Results: Among 35,286 individuals undergoing bariatric surgery, the mean (standard deviation) age was 47.9 (13.3) years, while 75.1% were female and 62.1% were white. A total of 6,067 individuals (17.2%) initiated GLP-1s after surgery, with approximately 22% beginning within two years of surgery, and the remainder initiating during post-surgical years 3-4 (36%), years 5-6 (27%) or beyond (14%). The overall median BMI before GLP-1 initiation was 37.5 kg/m2 (interquartile range 33.1 – 42.1). In regression models, females (adjusted hazard ratio [aHR] 1.82, 95% confidence intervals [CI] 1.69 to 1.96) and those undergoing sleeve gastrectomy (aHR 1.57, CI 1.48 to 1.67) were more likely to initiate GLP-1 than their counterparts. Each 1 kg/m2 increase in post-surgical BMI was associated with a 7% increase in likelihood of GLP-1 initiation (aHR 1.07, CI 1.07 to 1.08).
Conclusion: Among individuals undergoing bariatric surgery, approximately one in eight initiated a GLP-1. Initiation was greater among women, those undergoing sleeve gastrectomy and individuals with larger BMI regain than among their counterparts
DEVELOPMENT AND VALIDATION OF A MODERN PRESCRIPTION-BASED RISK SCORE TO PREDICT HEALTHCARE SPENDING
No full textPrescription-drug based risk scores offer an important alternative to diagnosis-based risk scoring systems when diagnostic information is unavailable; however, their value depends upon a given score’s ability to capture the current therapeutic landscape. We performed a retrospective cohort study using Merative MarketScan administrative claims data from continuously enrolled, commercially insured adults between January 2021 and December 2022 to develop and validate a modern, prescription-based risk score for predicting healthcare expenditures. Prescription use was described using over 300 binary drug categories, and total healthcare spending was the primary outcome. We characterized the cohort with descriptive statistics and fit several machine learning models that vary in their approaches to regularization and decision-making, including elastic net regression, random forest, and extreme gradient boosting, using 60% of the sample for model development and 40% for validation. Predictor weights were assigned based on beta coefficients from the elastic net regression model, with expenditures modeled on a logarithmic scale. The drug-only risk score achieved an R2 of 0.135 in the validation dataset, improving to 0.173 with the addition of age and sex. These results are comparable to many existing prescription-based risk scores predicting future total healthcare expenditures. Our findings underscore the potential of updated prescription-based risk scores for expenditure prediction and support further research to optimize model performance
USE OF GLUCAGON-LIKE PEPTIDE 1 AGONISTS (GLP-1s) AMONG INDIVIDUALS UNDERGOING BARIATRIC SURGERY IN THE UNITED STATES: A RETROSPECTIVE COHORT STUDY
Full text linkImportance: Although randomized and well-controlled observational studies demonstrate the efficacy of glucagon-like peptide 1 agonists (GLP-1s) for weight management after bariatric surgery, little is known regarding the frequency and predictors of such use.
Objective: To characterize the use and factors associated with GLP-1 initiation among U.S. adults undergoing bariatric surgery.
Design: Retrospective cohort study.
Setting: National multicenter database of electronic health records of ~113 million U.S. adults.
Participants: Adults undergoing bariatric surgery from 2015 to 2021 who did not use GLP-1s during the 12-months prior to surgery.
Exposures: Sociodemographic (age, sex, race, region, etc) and clinical (bariatric surgery procedures, body mass index [BMI], comorbidities, co-medications) factors.
Measurements: We first used descriptive statistics to characterize GLP-1 initiation after bariatric surgery. We then used Cox proportional hazards models to identify baseline patient characteristics associated with GLP-1 initiation. We also used time-dependent Cox models to examine the association of post-surgery BMI with GLP-1 initiation.
Results: Among 35,286 individuals undergoing bariatric surgery, the mean (standard deviation) age was 47.9 (13.3) years, while 75.1% were female and 62.1% were white. A total of 6,067 individuals (17.2%) initiated GLP-1s after surgery, with approximately 22% beginning within two years of surgery, and the remainder initiating during post-surgical years 3-4 (36%), years 5-6 (27%) or beyond (14%). The overall median BMI before GLP-1 initiation was 37.5 kg/m2 (interquartile range 33.1 – 42.1). In regression models, females (adjusted hazard ratio [aHR] 1.82, 95% confidence intervals [CI] 1.69 to 1.96) and those undergoing sleeve gastrectomy (aHR 1.57, CI 1.48 to 1.67) were more likely to initiate GLP-1 than their counterparts. Each 1 kg/m2 increase in post-surgical BMI was associated with a 7% increase in likelihood of GLP-1 initiation (aHR 1.07, CI 1.07 to 1.08).
Conclusion: Among individuals undergoing bariatric surgery, approximately one in eight initiated a GLP-1. Initiation was greater among women, those undergoing sleeve gastrectomy and individuals with larger BMI regain than among their counterparts
HETEROGENEITY OF TREATMENT EFFECTS OF GLUCAGON-LIKE PEPTIDE-1 (GLP-1) RECEPTOR AGONISTS ON WEIGHT LOSS: A RETROSPECTIVE COHORT STUDY
Full text linkBackground: While there is high quality evidence supporting the effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1) for the treatment of obesity, less is known regarding how such effectiveness may vary across different patient subpopulations.
Objectives: To quantify heterogeneity in weight loss response among GLP-1 users, stratified by patient age, sex, race/ethnicity, diabetes, and baseline body mass index (BMI).
Methods: We used TriNetX, a database containing electronic health records from 81 academic medical centers in the United States, to identify adults with at least 6-month continuous GLP-1 use between September 2014 and November 2023. Our primary outcome was percentage change in BMI from baseline, defined as the most recent BMI measurement within 6 months prior to GLP-1 initiation, overall and across different subpopulations of interest. We used linear mixed-effects models with natural splines to examine BMI changes over time, adjusting for individuals’ demographics and clinical characteristics.
Results: Among 23,291 GLP-1 users, the mean baseline BMI was 37.3 ± 7.7 kg/m² and 65.2% were female. During the 6-month follow-up period, 42% achieved ≥5% BMI reduction. There was no statistically significant reduction in BMI between older (≥65 years) and younger adults (-4.1% vs. -4.7%, p=0.132). There were modest, though statistically significant, differences in BMI reduction by sex (females: -5.1% vs males: -3.5%, p<0.001) and race (Black: -4.1% vs White: -4.8%, p<0.001). Individuals with no diabetes experienced substantially greater weight loss than patients with diabetes (-6.7% vs -3.5%, p<0.001). Compared to patients with baseline BMI<30 (-2.0%), patients with BMI 30-35 showed greater reduction (-4.5%, p<0.001), and those with BMI≥35 showed the largest reduction (-5.2%, p<0.001).
Conclusions: Among this large, diverse cohort of adults in the United States, real-world effectiveness of GLP-1 was greater among women, Whites, individuals without diabetes, and those with higher baseline BMI. These findings can be used to inform further research as well as treatment selection among those who may be eligible for pharmacologic treatment of obesity
Comparative Effectiveness of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on the Risk of Dementia in Patients with Type 2 Diabetes and Hypertension
No full textObjectives: Specific aims of the study were: (1) To develop RxDx risk index to predict dementia in patients with type 2 diabetes mellitus and hypertension (2) To compare RxDx risk index with different versions of Charlson comorbidity score (CCS) and chronic disease score (CDS) to predict dementia and (3) To compare Angiotensin Converting Enzyme (ACE) inhibitors versus Angiotensin Receptor Blockers (ARB) for the risk of dementia in patients with type 2 diabetes mellitus and hypertension.
Methods: The Clinical Practice Research database was used for this retrospective longitudinal cohort study. Elderly patients (age>=65 years) diagnosed with type 2 diabetes and hypertension without prior diagnosis for dementia were included in the cohort. The Cox proportional hazard model was constructed to model time to dementia by incorporating age, gender and 31 RxDx disease conditions. Points were assigned to risk factors based on beta coefficients to obtain summary risk score. Different rick indices were compared against RxDx-Dementia risk index using c statistics, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). A marginal structural model was constructed while controlling for demographic and clinical baseline variables and time-varying blood pressure variable to estimate causal effect of ACE inhibitors compared to ARB on the risk of dementia.
Results: The incidence of dementia was 3.42% in patients with type 2 diabetes mellitus and hypertension. The c-statistics value for RxDx-Dementia risk index was 0.795 (95% confidence interval [CI], 0.789-0.801) and 0.806 (95% CI, 0.798-0.814). Based on the c-statisctics, NRI and IDI values the RxDx-Dementia risk index performed better compared to summary CCS, CDS scores and its combinations. The marginal structural model estimated statistically significant 39% (OR, 0.61; 95%CI, 0.50-0.77) reduction in the risk of developing dementia compared to ACE inhibitors.
Conclusions: RxDx-Dementia risk index can be a useful tool to identify hypertensive diabetic patients who are at high risk of developing dementia as well as to control confounding in observational studies. ARB may offer protective effect on the risk of dementia compared to ACE inhibitors in patients with type 2 diabetes and hypertension. When there is no treatment available for dementia, prevention or delaying onset of dementia may help reduce the overall disease burden.Pharmacy, College o
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