Incidence, Prevalence, and Racial and Ethnic Distribution of Inflammatory Bowel Disease in the United States.

BACKGROUND & AIMS: We sought to estimate the incidence, prevalence, and racial-ethnic distribution of physician-diagnosed inflammatory bowel disease (IBD) in the United States. METHODS: The study used 4 administrative claims data sets: a 20% random sample of national fee-for-service Medicare data (2007 to 2017); Medicaid data from Florida, New York, Pennsylvania, Ohio, and California (1999 to 2012); and commercial health insurance data from Anthem beneficiaries (2006 to 2018) and Optum's deidentified Clinformatics Data Mart (2000 to 2017). We used validated combinations of medical diagnoses, diagnostic procedures, and prescription medications to identify incident and prevalent diagnoses. We computed pooled age-, sex-, and race/ethnicity-specific insurance-weighted estimates and pooled estimates standardized to 2018 United States Census estimates with 95% confidence intervals (CIs). RESULTS: The age- and sex-standardized incidence of IBD per 100,000 person-years was 10.9 (95% CI, 10.6-11.2). The incidence of IBD peaked in the third decade of life, decreased to a relatively stable level across the fourth to eighth decades, and declined further. The age-, sex- and insurance-standardized prevalence of IBD was 721 per 100,000 population (95% CI, 717-726). Extrapolated to the 2020 United States Census, an estimated 2.39 million Americans are diagnosed with IBD. The prevalence of IBD per 100,000 population was 812 (95% CI, 802-823) in White, 504 (95% CI, 482-526) in Black, 403 (95% CI, 373-433) in Asian, and 458 (95% CI, 440-476) in Hispanic Americans. CONCLUSIONS: IBD is diagnosed in >0.7% of Americans. The incidence peaks in early adulthood and then plateaus at a lower rate. The disease is less commonly diagnosed in Black, Asian, and Hispanic Americans.

Validating claims-based definitions for deprescribing: Bridging the gap between clinical and administrative data.

BACKGROUND: Limited research has evaluated the validity of claims-based definitions for deprescribing. OBJECTIVES: Evaluate the validity of claims-based definitions of deprescribing against electronic health records (EHRs) for deprescribing of benzodiazepines (BZDs) after a fall-related hospitalization. METHODS: We used a novel data linkage between Medicare fee-for-service (FFS) and Part D with our health system's EHR. We identified patients aged ≥66 years with a fall-related hospitalization, continuous enrollment in Medicare FFS and Part D for 6 months pre- and post-hospitalization, and ≥2 BZD fills in the 6 months pre-hospitalization. Using a standardized EHR abstraction tool, we adjudicated deprescribing for a sub-sample with a fall-related hospitalization at UNC. We evaluated the validity of claims-based deprescribing definitions (e.g., gaps in supply, dosage reductions) versus chart review using sensitivity and specificity. RESULTS: Among 257 patients in the overall sample, 44% were aged 66-74 years, 35% had Medicare low-income subsidy, 79% were female. Among claims-based definitions using gaps in supply, the prevalence of BZD deprescribing ranged from 8.2% (no refills) to 36.6% (30-day gap). When incorporating dosage, the prevalence ranged from 55.3% to 65.8%. Among the validation sub-sample (n = 47), approximately one-third had BZDs deprescribed in the EHR. Compared to EHR, gaps in supply from claims had good sensitivity, but poor specificity. Incorporating dosage increased sensitivity, but worsened specificity. CONCLUSIONS: The sensitivity of claims-based definitions for deprescribing of BZDs was low; however, the specificity of a 90-day gap was >90%. Replication in other EHRs and for other low-value medications is needed to guide future deprescribing research.

Translation of a Claims-Based Frailty Index From the International Classification of Diseases, Ninth Revision, Clinical Modification to the Tenth Revision.

The Faurot frailty index (FFI) is a validated algorithm that uses enrollment and International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-based billing information from Medicare claims data as a proxy for frailty. In October 2015, the US health-care system transitioned from the ICD-9-CM to the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). Applying the Centers for Medicare and Medicaid Services General Equivalence Mappings, we translated diagnosis-based frailty indicator codes from the ICD-9-CM to the ICD-10-CM, followed by manual review. We used interrupted time-series analysis of Medicare data to assess the comparability of the pre- and posttransition FFI scores. In cohorts of beneficiaries enrolled in January 2015-2017 with 8-month frailty look-back periods, we estimated associations between the FFI and 1-year risk of aging-related outcomes (mortality, hospitalization, and admission to a skilled nursing facility). Updated indicators had similar prevalences as pretransition definitions. The median FFI scores and interquartile ranges (IQRs) for the predicted probability of frailty were similar before and after the International Classification of Diseases transition (pretransition: median, 0.034 (IQR, 0.02-0.07); posttransition: median, 0.038 (IQR, 0.02-0.09)). The updated FFI was associated with increased risks of mortality, hospitalization, and skilled nursing facility admission, similar to findings from the ICD-9-CM era. Studies of medical interventions in older adults using administrative claims should use validated indices, like the FFI, to mitigate confounding or assess effect-measure modification by frailty.

Burden and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States: Update 2021.

BACKGROUND & AIMS: Gastrointestinal diseases account for considerable health care use and expenditures. We estimated the annual burden, costs, and research funding associated with gastrointestinal, liver, and pancreatic diseases in the United States. METHODS: We generated estimates using data from the National Ambulatory Medical Care Survey; National Hospital Ambulatory Medical Care Survey; Nationwide Emergency Department Sample; National Inpatient Sample; Kids' Inpatient Database; Nationwide Readmissions Database; Surveillance, Epidemiology, and End Results program; National Vital Statistics System; Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research; MarketScan Commercial Claims and Encounters data; MarketScan Medicare Supplemental data; United Network for Organ Sharing registry; Medical Expenditure Panel Survey; and National Institutes of Health (NIH). RESULTS: Gastrointestinal health care expenditures totaled $119.6 billion in 2018. Annually, there were more than 36.8 million ambulatory visits for gastrointestinal symptoms and 43.4 million ambulatory visits with a primary gastrointestinal diagnosis. Hospitalizations for a principal gastrointestinal diagnosis accounted for more than 3.8 million admissions, with 403,699 readmissions. A total of 22.2 million gastrointestinal endoscopies were performed, and 284,844 new gastrointestinal cancers were diagnosed. Gastrointestinal diseases and cancers caused 255,407 deaths. The NIH supported $3.1 billion (7.5% of the NIH budget) for gastrointestinal research in 2020. CONCLUSIONS: Gastrointestinal diseases are responsible for millions of health care encounters and hundreds of thousands of deaths that annually costs billions of dollars in the United States. To reduce the high burden of gastrointestinal diseases, focused clinical and public health efforts, supported by additional research funding, are warranted.

Vedolizumab Is Associated With a Lower Risk of Serious Infections Than Anti-Tumor Necrosis Factor Agents in Older Adults.

BACKGROUND & AIMS: Despite the increased numbers of older adults with inflammatory bowel diseases (IBDs), there are few studies regarding the safety and effectiveness of IBD treatments in older adults. The aim of this study was to compare the safety and effectiveness of anti-tumor necrosis factor (TNF)-α agents and vedolizumab in older adults with IBD. METHODS: We conducted a retrospective cohort study using an active comparator, new-user design for adults age 65 years and older with IBD initiating anti-TNF-α agents and vedolizumab in the Medicare claims database from 2014 to 2017. The primary safety outcome was infection-related hospitalization (excluding intra-abdominal and perianal abscesses). Co-primary outcomes to estimate effectiveness were IBD-related hospitalization, IBD-related surgery, and new corticosteroid use 60 days or more after biologic initiation. We performed propensity score weighting to control for confounding and estimated adjusted hazard ratios and 95% confidence intervals using standardized morbidity ratio-weighted variables. RESULTS: We identified 1152 anti-TNF-α new users and 480 vedolizumab new users. The median age was 71 years in both cohorts and 11% were age 80 years or older. Crohn's disease patients comprised 54% of the anti-TNF-α cohort and 57% of the vedolizumab cohort. There was no significant difference in demographics, health care utilization, or frailty in both cohorts. More than half of both cohorts had a Charlson comorbidity index of 2 or higher. Vedolizumab users had a decreased risk of infection-related hospitalization (adjusted hazard ratio, 0.47; 95% confidence interval, 0.25-0.86). There was no significant difference in the outcomes approximating effectiveness. CONCLUSIONS: Older IBD patients treated with vedolizumab had a lower risk of infection-related hospitalization compared with those initiating anti-TNFs. We observed no difference in effectiveness defined by hospitalizations, surgery, or new corticosteroid use.

Impacts of Initial Prescription Length and Prescribing Limits on Risk of Prolonged Postsurgical Opioid Use.

BACKGROUND: In response to concerns about opioid addiction following surgery, many states have implemented laws capping the days supplied for initial postoperative prescriptions. However, few studies have examined changes in the risk of prolonged opioid use associated with the initial amount prescribed. OBJECTIVE: The objective of this study was to estimate the risk of prolonged opioid use associated with the length of initial opioid prescribed and the potential impact of prescribing limits. RESEARCH DESIGN: Using Medicare insurance claims (2007-2017), we identified opioid-naive adults undergoing surgery. Using G-computation methods with logistic regression models, we estimated the risk of prolonged opioid use (≥1 opioid prescription dispensed in 3 consecutive 30-d windows following surgery) associated with the varying initial number of days supplied. We then estimate the potential reduction in cases of prolonged opioid use associated with varying prescribing limits. RESULTS: We identified 1,060,596 opioid-naive surgical patients. Among the 70.0% who received an opioid for postoperative pain, 1.9% had prolonged opioid use. The risk of prolonged use increased from 0.7% (1 d supply) to 4.4% (15+ d). We estimated that a prescribing limit of 4 days would be associated with a risk reduction of 4.84 (3.59, 6.09)/1000 patients and would be associated with 2255 cases of prolonged use potentially avoided. The commonly used day supply limit of 7 would be associated with a smaller reduction in risk [absolute risk difference=2.04 (-0.17, 4.25)/1000]. CONCLUSIONS: The risk of prolonged opioid use following surgery increased monotonically with increasing prescription duration. Common prescribing maximums based on days supplied may impact many patients but are associated with relatively low numbers of reduced cases of prolonged use. Any prescribing limits need to be weighed against the need for adequate pain management.

Considerations for observational study design: Comparing the evidence of opioid use between electronic health records and insurance claims.

PURPOSE: Pharmacoepidemiology studies often use insurance claims and/or electronic health records (EHR) to capture information about medication exposure. The choice between these data sources has important implications. METHODS: We linked EHR from a large academic health system (2015-2017) to Medicare insurance claims for patients undergoing surgery. Drug utilization was characterized based on medication order dates in the EHR, and prescription fill dates in Medicare claims. We compared opioid use documented in EHR orders to prescription claims in four time periods: 1) Baseline (182 days before surgery); 2) Perioperative period; 3) Discharge date; 4) Follow-up (90 days after surgery). RESULTS: We identified 11 128 patients undergoing surgery. During baseline, 34.4% (EHR) versus 44.1% (claims) had evidence of opioid use, and 56.9% of all baseline use was reflected only in one data source. During the perioperative period, 78.8% (EHR) versus 47.6% (claims) had evidence of use. On the day of discharge, 59.6% (EHR) versus 45.5% (claims) had evidence of use, and 51.8% of all discharge use was reflected only in one data source. During follow-up, 4.3% (EHR) versus 10.4% (claims) were identified with prolonged opioid use following surgery with 81.4% of all prolonged use reflected only in one data source. CONCLUSIONS: When characterizing opioid exposure, we found substantial discrepancies between EHR medication orders and prescription claims data. In all time periods assessed, most patients' use was reflected only in the EHR, or only in the claims, not both. The potential for misclassification of drug utilization must be evaluated carefully, and choice of data source may have large impacts on key study design elements.

Trends in the use of disease-modifying therapies among reproductive-aged women with multiple sclerosis in the United States from 2010 to 2019.

PURPOSE: Multiple sclerosis (MS) is a chronic disease of the central nervous system that disproportionately affects women, with typical onset during reproductive age. Several disease-modifying therapies (DMTs) are FDA-approved to slow disease progression, but are not indicated for use during pregnancy. Our objective was to describe trends over time (2010-2019) in monthly point prevalence of DMT use among reproductive-age women, overall and by generic name. METHODS: This study used administrative claims data from the US during 2009-2019 to identify women age 15-44 with MS and continuous insurance coverage for ≥12 months. DMTs were identified using prescription fills and procedural claims for alemtuzumab, daclizumab, dimethyl fumarate, fingolimod, glatiramer acetate, interferon beta, mitoxantrone, natalizumab, ocrelizumab, and teriflunomide. Monthly prevalent use was defined as ≥1 days' supply of a DMT in the month. Age- and region-standardized monthly prevalence was estimated nonparametrically. RESULTS: Among 42 281 reproductive-aged women over 818 179 person-months, DMT use increased from a minimum monthly prevalence of 49.3% (February, 2011) to a maximum of 58.7% (April, 2019). In 2010, prevalence of injectable DMTs was 43.1% compared to 2.5% for oral DMTs; by 2014, however, oral DMTs (26.5%) surpassed injectable DMTs (23.7%) as the most common route of administration. In the most recent data available (December, 2019), the most common DMTs were dimethyl fumarate, glatiramer acetate, and fingolimod. CONCLUSIONS: DMT use among reproductive-aged women has rapidly evolved during the past decade. Collaborative treatment decision making between women with MS and clinicians may help optimize MS care and improve DMT uptake during reproductive years.

Comparative Effectiveness and Harms of Antibiotics for Outpatient Diverticulitis : Two Nationwide Cohort Studies.

BACKGROUND: Outpatient diverticulitis is commonly treated with either a combination of metronidazole and a fluoroquinolone (metronidazole-with-fluoroquinolone) or amoxicillin-clavulanate alone. The U.S. Food and Drug Administration advised that fluoroquinolones be reserved for conditions with no alternative treatment options. The comparative effectiveness of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for diverticulitis is uncertain. OBJECTIVE: To determine the effectiveness and harms of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for outpatient diverticulitis. DESIGN: Active-comparator, new-user, retrospective cohort studies. SETTING: Nationwide population-based claims data on U.S. residents aged 18 to 64 years with private employer-sponsored insurance (2000 to 2018) or those aged 65 years or older with Medicare (2006 to 2015). PARTICIPANTS: Immunocompetent adults with diverticulitis in the outpatient setting. INTERVENTION: Metronidazole-with-fluoroquinolone or amoxicillin-clavulanate. MEASUREMENTS: 1-year risks for inpatient admission, urgent surgery, and Clostridioides difficile infection (CDI) and 3-year risk for elective surgery. RESULTS: In MarketScan (IBM Watson Health), new users of metronidazole-with-fluoroquinolone (n = 106 361) and amoxicillin-clavulanate (n = 13 160) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [95% CI, -0.3 to 0.6]), 1-year urgent surgery risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]), 3-year elective surgery risk (risk difference, 0.2 percentage points [CI, -0.3 to 0.7]), or 1-year CDI risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]) between groups. In Medicare, new users of metronidazole-with-fluoroquinolone (n = 17 639) and amoxicillin-clavulanate (n = 2709) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [CI, -0.7 to 0.9]), 1-year urgent surgery risk (risk difference, -0.2 percentage points [CI, -0.6 to 0.1]), or 3-year elective surgery risk (risk difference, -0.3 percentage points [CI, -1.1 to 0.4]) between groups. The 1-year CDI risk was higher for metronidazole-with-fluoroquinolone than for amoxicillin-clavulanate (risk difference, 0.6 percentage points [CI, 0.2 to 1.0]). LIMITATION: Residual confounding is possible, and not all harms associated with these antibiotics, most notably drug-induced liver injury, could be assessed. CONCLUSION: Treating diverticulitis in the outpatient setting with amoxicillin-clavulanate may reduce the risk for fluoroquinolone-related harms without adversely affecting diverticulitis-specific outcomes. PRIMARY FUNDING SOURCE: National Institutes of Health.

Quantifying cumulative anticholinergic and sedative drug load among US Medicare Beneficiaries.

PURPOSE: Medications with anticholinergic and sedative properties are widely used among older adults despite strong evidence of harm. The drug burden index (DBI), a pharmacological screening tool, measures these properties across drug classes, and higher DBI drug exposure (DBI > 1) has been associated with certain physical function-related adverse events. Our aim was to quantify mean daily DBI drug exposure among older adults in the United States (US). METHODS: We screened medications for DBI properties and operationalized the DBI for US Medicare claims. We then conducted a retrospective cohort study of a 20% random, nationwide sample of 4 137 384 fee-for-service Medicare beneficiaries aged 66+ years (134 757 039 person-months) from January 2013 to December 2016. We measured the monthly distribution based on mean daily DBI, categorized as (a) >0 vs 0 (any use) and (b) 0, 0 < DBI ≤ 1, 1 < DBI ≤ 2, and DBI > 2, and examined temporal trends. We described patient-level factors (eg, demographics, healthcare use) associated with high (>2) vs low (0 < DBI≤1) DBI drug exposure. RESULTS: The distribution of the mean daily DBI, aggregated at the month-level, was: 58.1% DBI = 0, 29.0% 0 < DBI≤1, 9.3% 1 < DBI≤2, and 3.7% DBI > 2. Predictors of high monthly DBI drug exposure (DBI > 2) included certain indicators of increased healthcare use (eg, high number of drug claims), white race, younger age, frailty, and a psychosis diagnosis code. CONCLUSIONS: The predictors of high DBI drug exposure can inform discussions between patients and providers about medication appropriateness and potential de-prescribing. Future Medicare-based studies should assess the association between the DBI and adverse events.

Day-of-Surgery Gabapentinoids and Prolonged Opioid Use: A Retrospective Cohort Study of Medicare Patients Using Electronic Health Records.

BACKGROUND: While preoperative gabapentinoids are commonly used in surgical multimodal analgesia protocols, little is known regarding the effects this therapy has on prolonged postsurgical opioid use. In this observational study, we used data from a large integrated health care system to estimate the association between preoperative day-of-surgery gabapentinoids and the risk of prolonged postsurgical opioid use. METHODS: We identified adults age ≥65 years undergoing major therapeutic surgical procedures from a large integrated health care system from 2016 to 2019. Exposure to preoperative gabapentinoids on the day of surgery was measured using inpatient medication administration records, and the outcome of prolonged opioid use was measured using outpatient medication orders. We used stabilized inverse probability of treatment-weighted log-binomial regression to estimate risk ratios and 95% confidence intervals (CIs) of prolonged opioid use, comparing patients who received preoperative gabapentinoids to those who did not and adjusting for relevant clinical factors. The main analysis was conducted in the overall surgical population, and a secondary analysis was conducted among procedures where at least 30% of all patients received a preoperative gabapentinoid. RESULTS: Overall, 13,958 surgical patients met inclusion criteria, of whom 21.0% received preoperative gabapentinoids. The observed 90-day risk of prolonged opioid use following surgery was 0.91% (95% CI, 0.77-1.08). Preoperative gabapentinoid administration was not associated with a reduced risk of prolonged opioid use in the main analysis conducted in a broad surgical population (adjusted risk ratio [adjRR], 1.19 [95% CI, 0.67-2.12]) or in the secondary analysis conducted in patients undergoing colorectal resection, hip arthroplasty, knee arthroplasty, or hysterectomy (adjRR, 1.01 [95% CI, 0.30-3.33]). CONCLUSIONS: In a large integrated health system, we did not find evidence that preoperative gabapentinoids were associated with reduced risk of prolonged opioid use in patients undergoing a broad range of surgeries.

Trends in Opioid and Psychotropic Prescription in Pregnancy in the United States From 2001 to 2015 in a Privately Insured Population : A Cross-sectional Study.

BACKGROUND: Opioid and psychotropic prescriptions are common during pregnancy. Little is known about coprescriptions of both medications in this setting. OBJECTIVE: To describe opioid prescription among women who are prescribed psychotropics compared with women who are not. DESIGN: Cross-sectional study. SETTING: U.S. commercial insurance beneficiaries from MarketScan (2001 to 2015). PARTICIPANTS: Pregnant women at 22 weeks' gestation or greater who were insured continuously for 3 months or more before pregnancy through delivery. MEASUREMENTS: Opioid prescription, dosage thresholds (morphine milligram equivalents [MME] of ≥50/day and ≥90/day), number of opioid agents (≥2), and duration (≥30 days) among those with and without prescription of psychotropics, from 2011 to 2015. RESULTS: Among 958 980 pregnant women, 10% received opioids only, 6% psychotropics only, and 2% opioids with coprescription of psychotropics. Opioid prescription was higher among women prescribed psychotropics versus those who were not (26.5% vs. 10.7%). From 2001 to 2015, psychotropic prescription overall increased from 4.4% to 7.6%, opioid prescription without coprescription of psychotropics decreased from 11.9% to 8.4%, and opioids with coprescription decreased from 28.1% to 22.0%. Morphine milligram equivalents of 50 or greater per day decreased for women with and without coprescription (29.6% to 17.3% and 22.8% to 18.5%, respectively); MME of 90 or greater per day also decreased in both groups (15.0% to 4.7% and 11.5% to 4.2%, respectively). Women prescribed opioids only were more likely to have an antepartum hospitalization compared with those with neither prescription, as were women with coprescription versus those prescribed psychotropics only. Compared with those prescribed opioids only, women with coprescriptions were more likely to exceed MME of 90 or greater per day and to be prescribed 2 or more opioid agents and for 30 days or longer. Number and duration of opioids increased with benzodiazepine and gabapentin coprescription. LIMITATION: Inability to determine appropriateness of prescribing or overdose events. CONCLUSION: Opioids are frequently coprescribed with psychotropic medication during pregnancy and are associated with antepartum hospitalization. A substantial proportion of pregnant women are prescribed opioids at doses that increase overdose risk and exceed daily recommendations. PRIMARY FUNDING SOURCE: None.

Burden and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States: Update 2018.

BACKGROUND & AIMS: Estimates of disease burden can inform national health priorities for research, clinical care, and policy. We aimed to estimate health care use and spending among gastrointestinal (GI) (including luminal, liver, and pancreatic) diseases in the United States. METHODS: We estimated health care use and spending based on the most currently available administrative claims from commercial and Medicare Supplemental plans, data from the GI Quality Improvement Consortium Registry, and national databases. RESULTS: In 2015, annual health care expenditures for gastrointestinal diseases totaled $135.9 billion. Hepatitis ($23.3 billion), esophageal disorders ($18.1 billion), biliary tract disease ($10.3 billion), abdominal pain ($10.2 billion), and inflammatory bowel disease ($7.2 billion) were the most expensive. Yearly, there were more than 54.4 million ambulatory visits with a primary diagnosis for a GI disease, 3.0 million hospital admissions, and 540,500 all-cause 30-day readmissions. There were 266,600 new cases of GI cancers diagnosed and 144,300 cancer deaths. Each year, there were 97,700 deaths from non-malignant GI diseases. An estimated 11.0 million colonoscopies, 6.1 million upper endoscopies, 313,000 flexible sigmoidoscopies, 178,400 upper endoscopic ultrasound examinations, and 169,500 endoscopic retrograde cholangiopancreatography procedures were performed annually. Among average-risk persons aged 50-75 years who underwent colonoscopy, 34.6% had 1 or more adenomatous polyps, 4.7% had 1 or more advanced adenomatous polyps, and 5.7% had 1 or more serrated polyps removed. CONCLUSIONS: GI diseases contribute substantially to health care use in the United States. Total expenditures for GI diseases are $135.9 billion annually-greater than for other common diseases. Expenditures are likely to continue increasing.

Perioperative opioid prescriptions associated with stress incontinence and pelvic organ prolapse surgery.

BACKGROUND: There is an opioid epidemic in the United States with a contributing factor of opioids being prescribed for postoperative pain after surgery. OBJECTIVE: Among women who underwent stress urinary incontinence and pelvic organ prolapse surgeries, our primary objective was to determine the proportion of women who filled perioperative opioid prescriptions and to compare factors associated with these opioid prescriptions. We also sought to assess the risk of prolonged opioid use through 1 year after stress urinary incontinence and pelvic organ prolapse surgeries. STUDY DESIGN: Using a population-based cohort of commercially insured individuals in the 2005-2015 IBM MarketScan databases, we identified opioid-naive women ≥18 years who underwent stress urinary incontinence and/or pelvic organ prolapse procedures based on Current Procedural Terminology codes. We defined the perioperative period as the window beginning 30 days before surgery extending until 7 days after surgery. Any filled opioid prescription in this window was considered a perioperative prescription. For our primary outcome, we reported the proportion of opioid-naive women who filled a perioperative opioid prescription and reported the median quantity dispensed in the perioperative period. We also assessed demographic and perioperative factors associated with perioperative opioid prescription fills. Previous studies have defined prolonged use as the proportion of women who fill an opioid prescription between 90 and 180 days after surgery. We report this estimate as well as continuous opioid use, defined as the proportion of women with ongoing monthly opioid prescriptions filled through 1 year after stress urinary incontinence and/or pelvic organ prolapse surgery. RESULTS: Among the 217,460 opioid-naive women who underwent urogynecologic surgery, 61,025 (28.1%) had pelvic organ prolapse and stress urinary incontinence surgeries, 85,575 (39.4%) had stress urinary incontinence surgery without pelvic organ prolapse surgery, and 70,860 (32.6%) had pelvic organ prolapse surgery without stress urinary incontinence surgery. Overall, 167,354 (77.0%) filled a perioperative opioid prescription, and the median quantity was 30 pills (interquartile range, 20-30). In a multivariate regression model, younger age, pelvic organ prolapse surgery with or without stress urinary incontinence surgery, abdominal route, hysterectomy, and mesh use remained significantly associated with opioid prescriptions filled. Among those with a filled perioperative opioid prescription, the risk of prolonged use defined as an opioid prescription filled between 90 and 180 days was 7.5% (95% confidence interval, 7.3-7.6). However, the risk of prolonged use defined as continuous use with at least 1 monthly opioid prescription filled after surgery was significantly lower: 1.2% (1.13-1.24), 0.32% (0.29-0.35), 0.06% (0.05-0.08), and 0.04% (0.02-0.05) at 60, 90, 180, and 360 days after surgery, respectively. CONCLUSION: Among privately insured, opioid-naive women undergoing stress urinary incontinence and/or pelvic organ prolapse surgery, 77% of women filled an opioid prescription with a median of 30 opioid pills prescribed. For prolonged use, 7.5% (95% confidence interval, 7.3-7.6) filled an opioid prescription within 90 to 180 days after surgery, but the rates of continuously filled opioid prescriptions were significantly lower at 0.06% (95% confidence interval, 0.05-0.08) at 180 days and 0.04% (95% confidence interval, 0.02-0.05) at 1 year after surgery.

No Increase in Risk of Acute Myocardial Infarction in Privately Insured Adults Prescribed Proton Pump Inhibitors vs Histamine-2 Receptor Antagonists (2002-2014).

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are commonly used medications. Recent studies reported an increased risk of acute myocardial infarction (MI) in PPI users vs non-users. We evaluated MI risk associated with PPIs compared with histamine-2 receptor antagonists (H2RAs) in privately insured adults in the United States. METHODS: Using administrative claims from commercial and Medicare Supplemental plans (2001-2014), we compared risk of MI in patients who started a new prescription for PPIs vs H2RAs. Enrollees were followed from their first prescription until MI, medication discontinuation, plan disenrollment, or December 31, 2014. MI was defined using hospital diagnosis codes. Risk differences (RD), risk ratios, and 95% confidence intervals (CIs) were estimated using Kaplan-Meier methods at 3, 12, and 36 months after treatment initiation. Standardized morbidity ratio weights were used to control measured confounding. Analyses were stratified by plan type (commercial vs Medicare Supplemental). RESULTS: We identified more than 5 million new users of prescription PPIs and H2RAs. Median follow-up time was 60 days for patients with commercial insurance and 96 days in patients with Medicare Supplemental insurance. The 12-month weighted risk of MI was low overall (approximately 2 cases per 1000 among patients in commercial plans; 8 per 1000 among patients in Medicare Supplemental plans). In the RD analysis, we found no significant differences in MI risk between patients who started PPIs vs H2RAs for the first 12 months, either in the commercial population (weighted RD per 1000, -0.08; 95% CI, -0.51 to 0.36) or the Medicare Supplemental population (weighted RD per 1000, -0.45; 95% CI, -1.53 to 0.58). CONCLUSION: In an analysis of administrative claims from commercial and Medicare Supplemental plans, we found no evidence that prescription PPIs increase risk of MI compared with prescription H2RAs. Physicians and patients should not avoid starting a PPI because of concerns related to MI risk.

Burden and Cost of Outpatient Hemorrhoids in the United States Employer-Insured Population, 2014.

INTRODUCTION: Although hemorrhoids are a common indication for seeking health care, there are no contemporary estimates of burden and cost. We examined data from an administrative claims database to estimate health care use and aggregate costs. METHODS: We conducted a cross-sectional study using the MarketScan Commercial Claims and Encounters Database for 2014. The analysis included 18.9 million individuals who were aged 18-64 and continuously enrolled with prescription coverage. Outpatient hemorrhoid claims were captured using the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes in the first position, as well as Common Procedural Terminology codes. Prescription medications were identified using National Drug Codes. Annual prevalence and costs were determined by summing gross payments for prescription medications, physician encounters, and facility costs. We used validated weights to standardize annual cost estimates to the US employer-insured population. RESULTS: In 2014, we identified 227,638 individuals with at least one outpatient hemorrhoid-related claim (annual prevalence, 1.2%). Among those, 119,120 had prescription medication claims, 136,125 had physician claims, and 28,663 had facility claims. After standardizing, we estimated that 1.4 million individuals in the US employer-insured population sought care for hemorrhoids in 2014 for a total annual cost of $770 million. This included $322 million in physician claims, $361 million in outpatient facility claims, and $88 million in prescription medication claims. CONCLUSIONS: The estimated economic burden of hemorrhoids in the employer-insured population approaches $800 million annually. Given the substantial and rising burden and cost, expanded research attention should be directed to hemorrhoidal etiology, prevention, and treatment.

Renin-Angiotensin-Aldosterone System-based Antihypertensive Agents and the Risk of Colorectal Cancer Among Medicare Beneficiaries.

BACKGROUND: Biologic evidence suggests that angiotensin II may play a role in tumor progression or growth. We compared the short-term colorectal cancer (CRC) risk among initiators of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) versus guideline-recommended clinical alternatives (beta blockers, calcium channel blockers [CCB], and thiazides). METHODS: We conducted a new-user cohort study on U.S. Medicare beneficiaries aged over 65 years, who initiated antihypertensive monotherapy during 2007-2013 and were free of cancer diagnosis before drug initiation. Follow-up began 6 months postinitiation to allow time for the diagnostic delay. We estimated hazard ratios (HR) with 95% confidence intervals (CI) using propensity score weighted Cox regression, overall and stratified by time since drug initiation, and 5-year cumulative risk differences (RD) using Kaplan-Meier estimator. We assessed the potential for unmeasured confounding using supplemental data from Medicare Current Beneficiary Survey. RESULTS: For analyses without censoring for treatment changes, we observed 532 CRC events among 111,533 ACEI/ARB initiators. After a median follow-up of 2.2 years (interquartile range: 1.0-3.7), CRC risk was similar between ACEI/ARB and active comparators, with adjusted HRs of 1.0 (95% CI = 0.85, 1.1) for ACEI/ARB versus beta blockers, 1.2 (95% CI = 0.97, 1.4) for ACEI/ARB versus CCB and 1.0 (95% CI = 0.80, 1.3) for ACEI/ARB versus thiazide. Five-year RDs and as-treated analyses, which censored follow-up at medication changes, produced similar findings. CONCLUSIONS: Based on real-world antihypertensive utilization patterns in Medicare beneficiaries, our study suggests no association between ACEI/ARB initiation and the short-term CRC risk.

Impact of metformin use on the cardiovascular effects of dipeptidyl peptidase-4 inhibitors: An analysis of Medicare claims data from 2007 to 2015.

AIMS: To examine the outcomes of dipeptidyl peptidase-4 (DPP-4) inhibitor initiation with and without concurrent metformin treatment. MATERIALS AND METHODS: We identified Medicare enrollees initiating a DPP-4 inhibitor, a sulphonylurea or a thiazolidinedione. Using propensity-score-weighted Poisson models, we evaluated 1-year cardiovascular (CV) outcome incidence among initiators of DPP-4 inhibitors versus comparators in subgroups with and without concurrent metformin use, and assessed the interaction between initiation drug and metformin. Outcomes included mortality, non-fatal myocardial infarction (MI), stroke, and a composite outcome. RESULTS: For the DPP-4 inhibitor (n = 13 391) versus sulphonylurea (n = 33 206) comparison, rate differences in composite outcome incidence favoured DPP-4 inhibitors: -2.0/100 person-years among metformin users (95% confidence interval [CI] -2.7 to -1.3) and - 1.0/100 person-years (95% CI -1.8 to -0.2) among metformin non-users. Similar rate difference trends among metformin users and non-users were seen for mortality (-1.5/100 person-years [95% CI -2.1 to -0.9] and -0.7/100 person-years [95% CI -1.4 to 0.0]) and non-fatal MI (-0.5/100 person-years [95% CI -0.8, -0.3] and 0.1/100 person-years [95% CI -0.2 to 0.4]). The interaction between DPP-4 inhibitor initiation and metformin was statistically significant for non-fatal MI (P = 0.008). For the DPP-4 inhibitor (n = 22 210) versus thiazolidinedione (n = 9517) comparison, rate differences in composite outcome incidence for DPP-4 inhibitor initiation were -0.6/100 person-years (95% CI -1.5 to 0.2) among metformin users and 1.0 (95% CI 0.0 to 2.0) among metformin non-users. Similar rate difference trends among metformin users and non-users were seen for mortality (-0.5/100 person-years [95% CI -1.3 to 0.1] and 0.8/100 person-years [95% CI -0.0 to 1.7]) and non-fatal MI (-0.1/100 person-years [95% CI -0.4 to 0.2] and 0.2/100 person-years [95% CI -0.1 to 0.6]). The interaction between DPP-4 inhibitor initiation and metformin was statistically significant for the composite outcome (P = 0.024) and mortality (P = 0.023). CONCLUSION: Incidence rate differences in multiple CV outcomes appeared more favourable when DPP-4 inhibitor initiation occurred in the presence of metformin, suggesting a possible interaction between DPP-4 inhibitors and metformin.

Study design choices for evaluating the comparative safety of diabetes medications: An evaluation of pioglitazone use and risk of bladder cancer in older US adults with type-2 diabetes.

AIM: The aim of the study was to empirically demonstrate the effect of varying study designs when evaluating the safety of pioglitazone in treating bladder cancer. METHODS: We identified Medicare beneficiaries above 65 years of age with diabetes between 2008 and 2015 and with classified exposure (at least two claims within 180 days) to glucose-lowering drugs (GLD), pioglitazone or another drug. The effects of varying the following study design parameters on bladder cancer risk were assessed: use of a new vs existing drug, choice of referent (all non-users and users of GLDs, non-insulin GLDs and DPP-4s) and whether or not censoring accounted for treatment change. We used the Cox proportional hazards model to obtain adjusted HRs and 95% CIs. RESULTS: We included 1,510,212 patients classified as pioglitazone users (N = 135,188) or non-users (N = 1,375,024). Users had more diabetic complications than non-users, but fewer than insulin users. The HR ranged from 1.10 (1.01-1.20) to 1.13 (0.99-1.29) when censoring ignored treatment change, suggesting a weak association or none between pioglitazone and bladder cancer, probably under-estimating risk. However, the HR was 1.20 (1.01-1.42) when cohorts were restricted to new users, censored upon treatment change, and when DPP-4 was used as the referent, suggesting an increased risk of bladder cancer associated with pioglitazone. CONCLUSIONS: The continued demand for new GLDs indicates the need for more robust observational methods to improve the value of generating real-world evidence in equipping clinicians to make informed prescribing decisions. Although there is no one-size-fits-all approach, we recommend active comparator new user study designs that compare therapeutically equivalent drugs and account for treatment changes during follow-up to present the least biased comparative safety estimates.

Sodium-glucose co-transporter-2 inhibitor use and risk of lower-extremity amputation: Evolving questions, evolving answers.

AIM: To examine whether sodium-glucose co-transporter-2 (SGLT2) inhibitors are associated with a higher risk of lower-extremity amputation than dipeptidyl-peptidase-4 (DPP-4) inhibitors and sulphonylureas. METHODS: We conducted a retrospective cohort study, using the MarketScan Commercial Claims and Encounters Database (2013-2015), to compare the incidence of lower-extremity amputation (LEA) between initiators of SGLT2 inhibitors and initiators of two second-line drugs, DPP-4 inhibitors and sulphonylureas (SUs). We estimated crude incidence rates (IRs) and adjusted hazard ratios (aHR), with 95% confidence intervals (CIs), before and after propensity-score weighting. We additionally conducted sensitivity analyses using a comparator group of all non-metformin, non-SGLT2 inhibitor glucose-lowering drugs, as previous studies used this approach. RESULTS: In a cohort of 328 150 individuals aged 18 to 64 years, the IR of LEA ranged from 1.5 to 2.4 per 1000 person-years. In as-treated analysis, the estimated hazard of LEA was increased among SGLT2 inhibitor initiators compared to DPP-4 inhibitor initiators (aHR 1.69, 95% CI 1.20-2.38), but not compared to SU initiators (aHR 1.02, 95% CI 0.67-1.55) or non-metformin, non-SGLT2 inhibitor initiators (aHR 1.02, 95% CI 0.54-1.93). Results were consistent in intention-to-treat analysis and across a number of sensitivity analyses. CONCLUSIONS: Among commercially insured patients in the United States, our results suggest that initiation of SGLT2 inhibitors may increase the risk of LEA compared to initiation of DPP-4 inhibitors. Contrasting results when comparing SGLT2 inhibitor initiators to DPP-4 inhibitor and SU initiators highlight the importance of choosing appropriate comparator drugs when addressing comparative effectiveness and safety questions that can inform clinical decision-making.