Publications

BACKGROUND: Paediatric obesity disproportionately impacts individuals from minoritized racial and ethnic backgrounds. Recent guidelines support use of anti-obesity pharmacotherapy for adolescents with obesity, but the potential impact on disparities in obesity prevalence has not been evaluated.

OBJECTIVES: To model changes in obesity prevalence with increasing utilization of anti-obesity pharmacotherapy among adolescents.

METHODS: Data representative of American adolescents ages 12-17 years were obtained from the National Health and Nutrition Examination Survey, cycles 2011 through pre-pandemic 2020. A body mass index (BMI) reduction of 16.7% was applied to each participant based on clinical trial results of weekly subcutaneous semaglutide 2.4 mg among adolescents. Utilization disparities were based on utilization of the same medication class among adults. Obesity prevalence was calculated assuming utilization of 10%-100%, stratified by race and ethnicity.

RESULTS: Among 4442 adolescents representing 26 247 384 American adolescents, projected overall obesity prevalence decreased from 22.2% to 8.4% with 100% utilization. However, disparities increased relative to Non-Hispanic White youth, with prevalence among Non-Hispanic Black and Mexican American youth ranging from 40%-60% higher to 90%-120% higher, respectively.

CONCLUSIONS: Increasing utilization of anti-obesity pharmacotherapy may widen relative disparities in obesity, particularly if utilization is unequal. Advocacy for equitable access is needed to minimize worsening of obesity-related disparities.

INTRODUCTION: Administrative health data could contribute to generalizable microscopic colitis insights, but International Classification of Diseases (ICD) codes for microscopic colitis have not been validated.

METHODS: We identified individuals who received care for diarrhea in the Veterans Health Administration and classified them by receipt of microscopic colitis ICD codes. We reviewed random samples of charts to calculate the positive predictive value (PPV) and negative predictive value (NPV). We then calculated the sensitivity and specificity in clinically relevant cohorts.

RESULTS: The PPV was 0.790 and the NPV was 0.995. In a cohort of individuals with diarrhea who underwent colonoscopy, the sensitivity and specificity were 0.734 and 0.996, respectively.

CONCLUSION: Alternative ascertainment methods for microscopic colitis are needed because ICD codes have suboptimal performance.

INTRODUCTION: Few studies have evaluated multitarget stool DNA (mt-sDNA) in clinical practice. We analyzed mt-sDNA utilization at the University of Pittsburgh Medical Center.

METHODS: We assessed mt-sDNA orders between January 1, 2017, and December 31, 2021. Data collection included electronic capture of mt-sDNA orders, completed stool submissions, and test results. Multivariable models were used to assess associations between mt-sDNA completion and results and age, sex, and race.

RESULTS: There were 91,664 mt-sDNA orders in 73,704 patients. A total of 54.7% (40,337/73,704) completed an mt-sDNA test, and 7,424 (18.6%) tested positive. Completion rates increased by age <50-59 years (N = 12,818; 48.2%), 60-69 years (14,982; 56.3%), and ≥70 years (N = 9,850; 55.6%) ( P < 0.0001). The completion rate for males (52.7%; 15,297/29,025) did not differ significantly from females (53.3%; 22,353/41,901) ( P = 0.09). By race, the completion rates of White patients (54.1%; 34,874/64,512) and Asian patients (56.9%; 493/867) were higher than those of Black patients (38.8%; 1,699/4,376) ( P < 0.0001). Test completion declined with repeat mt-sDNA orders, with ≤32% completion rate after ≥3 orders. In a multivariable model, older age was associated with greater likelihood of a positive test (odds ratio 1.22, 95% confidence interval 1.20-1.24, P < 0.0001), and Black patients had lower odds of a positive test (odds ratio 0.65, 95% confidence interval 0.56-0.76, P < 0.0001).

DISCUSSION: Only 54.7% of patients completed their mt-sDNA test order. Older individuals were more likely to complete testing and test positive. Black patients were less likely to complete testing and, unexpectedly, less likely to test positive. Further exploration of mt-sDNA utilization including better understanding of the determinants of uptake, appropriateness, and evaluation of outcomes at colonoscopy is needed.

BACKGROUND: Active surveillance pharmacovigilance is an emerging approach to identify medications with unanticipated effects. We previously developed a framework called pharmacopeia-wide association studies (PharmWAS) that limits false positive medication associations through high-dimensional confounding adjustment and set enrichment. We aimed to assess the transportability and generalizability of the PharmWAS framework by using medical claims data to reproduce known medication associations with Clostridioides difficile infection (CDI) or gastrointestinal bleeding (GIB).

METHODS: We conducted case-control studies using Optum's de-identified Clinformatics Data Mart Database of individuals enrolled in large commercial and Medicare Advantage health plans in the United States. Individuals with CDI (from 2010 to 2015) or GIB (from 2010 to 2021) were matched to controls by age and sex. We identified all medications utilized prior to diagnosis and analysed the association of each with CDI or GIB using conditional logistic regression adjusted for risk factors for the outcome and a high-dimensional propensity score.

FINDINGS: For the CDI study, we identified 55,137 cases, 220,543 controls, and 290 medications to analyse. Antibiotics with Gram-negative spectrum, including ciprofloxacin (aOR 2.83), ceftriaxone (aOR 2.65), and levofloxacin (aOR 1.60), were strongly associated. For the GIB study, we identified 450,315 cases, 1,801,260 controls, and 354 medications to analyse. Antiplatelets, anticoagulants, and non-steroidal anti-inflammatory drugs, including ticagrelor (aOR 2.81), naproxen (aOR 1.87), and rivaroxaban (aOR 1.31), were strongly associated.

INTERPRETATION: These studies demonstrate the generalizability and transportability of the PharmWAS pharmacovigilance framework. With additional validation, PharmWAS could complement traditional passive surveillance systems to identify medications that unexpectedly provoke or prevent high-impact conditions.

FUNDING: U.S. National Institute of Diabetes and Digestive and Kidney Diseases.

BACKGROUND: Paediatric obesity disproportionately impacts individuals from minoritized racial and ethnic backgrounds. Recent guidelines support use of anti-obesity pharmacotherapy for adolescents with obesity, but the potential impact on disparities in obesity prevalence has not been evaluated.

OBJECTIVES: To model changes in obesity prevalence with increasing utilization of anti-obesity pharmacotherapy among adolescents.

METHODS: Data representative of American adolescents ages 12-17 years were obtained from the National Health and Nutrition Examination Survey, cycles 2011 through pre-pandemic 2020. A body mass index (BMI) reduction of 16.7% was applied to each participant based on clinical trial results of weekly subcutaneous semaglutide 2.4 mg among adolescents. Utilization disparities were based on utilization of the same medication class among adults. Obesity prevalence was calculated assuming utilization of 10%-100%, stratified by race and ethnicity.

RESULTS: Among 4442 adolescents representing 26 247 384 American adolescents, projected overall obesity prevalence decreased from 22.2% to 8.4% with 100% utilization. However, disparities increased relative to Non-Hispanic White youth, with prevalence among Non-Hispanic Black and Mexican American youth ranging from 40%-60% higher to 90%-120% higher, respectively.

CONCLUSIONS: Increasing utilization of anti-obesity pharmacotherapy may widen relative disparities in obesity, particularly if utilization is unequal. Advocacy for equitable access is needed to minimize worsening of obesity-related disparities.

BACKGROUND: Paediatric obesity disproportionately impacts individuals from minoritized racial and ethnic backgrounds. Recent guidelines support use of anti-obesity pharmacotherapy for adolescents with obesity, but the potential impact on disparities in obesity prevalence has not been evaluated.

OBJECTIVES: To model changes in obesity prevalence with increasing utilization of anti-obesity pharmacotherapy among adolescents.

METHODS: Data representative of American adolescents ages 12-17 years were obtained from the National Health and Nutrition Examination Survey, cycles 2011 through pre-pandemic 2020. A body mass index (BMI) reduction of 16.7% was applied to each participant based on clinical trial results of weekly subcutaneous semaglutide 2.4 mg among adolescents. Utilization disparities were based on utilization of the same medication class among adults. Obesity prevalence was calculated assuming utilization of 10%-100%, stratified by race and ethnicity.

RESULTS: Among 4442 adolescents representing 26 247 384 American adolescents, projected overall obesity prevalence decreased from 22.2% to 8.4% with 100% utilization. However, disparities increased relative to Non-Hispanic White youth, with prevalence among Non-Hispanic Black and Mexican American youth ranging from 40%-60% higher to 90%-120% higher, respectively.

CONCLUSIONS: Increasing utilization of anti-obesity pharmacotherapy may widen relative disparities in obesity, particularly if utilization is unequal. Advocacy for equitable access is needed to minimize worsening of obesity-related disparities.

INTRODUCTION: Administrative health data could contribute to generalizable microscopic colitis insights, but International Classification of Diseases (ICD) codes for microscopic colitis have not been validated.

METHODS: We identified individuals who received care for diarrhea in the Veterans Health Administration and classified them by receipt of microscopic colitis ICD codes. We reviewed random samples of charts to calculate the positive predictive value (PPV) and negative predictive value (NPV). We then calculated the sensitivity and specificity in clinically relevant cohorts.

RESULTS: The PPV was 0.790 and the NPV was 0.995. In a cohort of individuals with diarrhea who underwent colonoscopy, the sensitivity and specificity were 0.734 and 0.996, respectively.

CONCLUSION: Alternative ascertainment methods for microscopic colitis are needed because ICD codes have suboptimal performance.

INTRODUCTION: Few studies have evaluated multitarget stool DNA (mt-sDNA) in clinical practice. We analyzed mt-sDNA utilization at the University of Pittsburgh Medical Center.

METHODS: We assessed mt-sDNA orders between January 1, 2017, and December 31, 2021. Data collection included electronic capture of mt-sDNA orders, completed stool submissions, and test results. Multivariable models were used to assess associations between mt-sDNA completion and results and age, sex, and race.

RESULTS: There were 91,664 mt-sDNA orders in 73,704 patients. A total of 54.7% (40,337/73,704) completed an mt-sDNA test, and 7,424 (18.6%) tested positive. Completion rates increased by age <50-59 years (N = 12,818; 48.2%), 60-69 years (14,982; 56.3%), and ≥70 years (N = 9,850; 55.6%) ( P < 0.0001). The completion rate for males (52.7%; 15,297/29,025) did not differ significantly from females (53.3%; 22,353/41,901) ( P = 0.09). By race, the completion rates of White patients (54.1%; 34,874/64,512) and Asian patients (56.9%; 493/867) were higher than those of Black patients (38.8%; 1,699/4,376) ( P < 0.0001). Test completion declined with repeat mt-sDNA orders, with ≤32% completion rate after ≥3 orders. In a multivariable model, older age was associated with greater likelihood of a positive test (odds ratio 1.22, 95% confidence interval 1.20-1.24, P < 0.0001), and Black patients had lower odds of a positive test (odds ratio 0.65, 95% confidence interval 0.56-0.76, P < 0.0001).

DISCUSSION: Only 54.7% of patients completed their mt-sDNA test order. Older individuals were more likely to complete testing and test positive. Black patients were less likely to complete testing and, unexpectedly, less likely to test positive. Further exploration of mt-sDNA utilization including better understanding of the determinants of uptake, appropriateness, and evaluation of outcomes at colonoscopy is needed.

BACKGROUND: Active surveillance pharmacovigilance is an emerging approach to identify medications with unanticipated effects. We previously developed a framework called pharmacopeia-wide association studies (PharmWAS) that limits false positive medication associations through high-dimensional confounding adjustment and set enrichment. We aimed to assess the transportability and generalizability of the PharmWAS framework by using medical claims data to reproduce known medication associations with Clostridioides difficile infection (CDI) or gastrointestinal bleeding (GIB).

METHODS: We conducted case-control studies using Optum's de-identified Clinformatics Data Mart Database of individuals enrolled in large commercial and Medicare Advantage health plans in the United States. Individuals with CDI (from 2010 to 2015) or GIB (from 2010 to 2021) were matched to controls by age and sex. We identified all medications utilized prior to diagnosis and analysed the association of each with CDI or GIB using conditional logistic regression adjusted for risk factors for the outcome and a high-dimensional propensity score.

FINDINGS: For the CDI study, we identified 55,137 cases, 220,543 controls, and 290 medications to analyse. Antibiotics with Gram-negative spectrum, including ciprofloxacin (aOR 2.83), ceftriaxone (aOR 2.65), and levofloxacin (aOR 1.60), were strongly associated. For the GIB study, we identified 450,315 cases, 1,801,260 controls, and 354 medications to analyse. Antiplatelets, anticoagulants, and non-steroidal anti-inflammatory drugs, including ticagrelor (aOR 2.81), naproxen (aOR 1.87), and rivaroxaban (aOR 1.31), were strongly associated.

INTERPRETATION: These studies demonstrate the generalizability and transportability of the PharmWAS pharmacovigilance framework. With additional validation, PharmWAS could complement traditional passive surveillance systems to identify medications that unexpectedly provoke or prevent high-impact conditions.

FUNDING: U.S. National Institute of Diabetes and Digestive and Kidney Diseases.