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

Comparative safety of pioglitazone versus clinically meaningful treatment alternatives concerning the risk of bladder cancer in older US adults with type 2 diabetes

Aims: To compare bladder cancer incidence between patients initiating pioglitazone treatment and patients initiating treatment with dipeptidyl-peptidase-4 inhibitors [DPP-4s] or sulfonylureas. Methods: We identified Medicare beneficiaries aged >65 years who initiated treatment with pioglitazone (N = 38 700), DPP-4s (N = 82 552) or sulfonylureas (N = 126 104) between 2007 and 2014 after at least 6 months without prescriptions for these drug classes. Patients were followed from second prescription until bladder cancer outcome (2 claims within 60 days) using a 6-month induction/latency period, censoring for treatment change, death or end of 2014. We used propensity score-weighted Cox proportional-hazards models to obtain adjusted hazard ratios (aHR) and their 95% confidence intervals. Results: Overall mean age of participants was 75 years and 41% were men. Over a median of 1.2 treatment years, 727 beneficiaries developed bladder cancer. Pioglitazone initiators had an increased incidence of bladder cancer (308 vs 204 [DPP-4s] or 231 [sulfonylureas] per 100 000 person-years; aHR, 1.57 [1.23-2.00] vs DPP-4s and 1.32 [1.02-1.70] vs sulfonylureas). The increased risk emerged within the first 2 years of treatment (aHR, 1.63 [1.22-2.17] vs DPP-4s and 1.32 [0.98-1.78] vs sulfonylureas). If treatment was discontinued within the first 2 years, the risk after 2 years post initiation was attenuated (aHR, 0.89 [0.61-1.28]) compared with patients treated for more than 2 years (aHR, 1.45 [0.93-2.26]) both vs DPP-4s. Findings were consistent across secondary and sensitivity analyses. Conclusions: Pioglitazone was associated with an elevated risk of bladder cancer compared with DPP-4s and sulfonylureas. The elevated risk emerged within the first 2 years of treatment and was attenuated after discontinuing. Pioglitazone's relative effectiveness should be weighed against a small absolute increase in risk of bladder cancer

Cost of Outpatient Arthroscopic Anterior Cruciate Ligament Reconstruction Among Commercially Insured Patients in the United States, 2005-2013

Background: Despite the significance of anterior cruciate ligament (ACL) injuries, these conditions have been under-researched from a population-level perspective. It is important to determine the economic effect of these injuries in order to document the public health burden in the United States. Purpose: To describe the cost of outpatient arthroscopic ACL reconstruction and health care utilization among commercially insured beneficiaries in the United States. Study Design: Economic and decision analysis; Level of evidence, 3. Methods: The study used the Truven Health Analytics MarketScan Commercial Claims and Encounters database, an administrative claims database that contains a large sample (approximately 148 million) of privately insured individuals aged <65 years and enrolled in employer-sponsored plans. All claims with Current Procedural Terminology (CPT) code 29888 (arthroscopically aided ACL reconstruction or augmentation) from 2005 to 2013 were included. “Immediate procedure” cost was computed assuming a 3-day window of care centered on date of surgery. “Total health care utilization” cost was computed using a 9-month window of care (3 months preoperative and 6 months postoperative). Results: There were 229,446 outpatient arthroscopic ACL reconstructions performed over the 9-year study period. Median immediate procedure cost was $9399.49. Median total health care utilization cost was$13,403.38. Patients who underwent concomitant collateral ligament (medial [MCL], lateral [LCL]) repair or reconstruction had the highest costs for both immediate procedure ($12,473.24) and health care utilization ($17,006.34). For patients who had more than 1 reconstruction captured in the database, total health care utilization costs were higher for the second procedure than the first procedure ($16,238.43 vs$15,000.36), despite the fact that immediate procedure costs were lower for second procedures ($8685.73 vs$9445.26). Conclusion: These results provide a foundation for understanding the public health burden of ACL injuries in the United States. Our findings suggest that further research on the prevention and treatment of ACL injuries is necessary to reduce this burden

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

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

Incidence of anterior cruciate ligament reconstruction among adolescent females in the United States, 2002 through 2014

In 1999, a landmark study reported that women were more likely thanmento sustain an anterior cruciate ligament (ACL) injury in sex-comparable collegiate sports. Since then, an extensive body of research has focused on understanding and addressing sex disparities inACL injuries. This study aimed to investigate time trends in ACL reconstruction among commercially insured individuals in the United States while focusing on sex differences among adolescentswith the goal of assessing the effectiveness of the intensive research and prevention efforts of the past 15 years in reducing the sex disparity in ACL injury incidence

Trends in Incidence of ACL Reconstruction and Concomitant Procedures Among Commercially Insured Individuals in the United States, 2002-2014

Background: Few population-based descriptive studies on the incidence of anterior cruciate ligament (ACL) reconstruction and concomitant pathology exist. Hypothesis: Incidence of ACL reconstruction has increased from 2002 to 2014. Study Design: Descriptive clinical epidemiology study. Level of Evidence: Level 3. Methods: The Truven Health Analytics MarketScan Commercial Claims and Encounters database, which contains insurance enrollment and health care utilization data for approximately 158 million privately insured individuals younger than 65 years, was used to obtain records of ACL reconstructions performed between 2002 and 2014 and any concomitant pathology using Current Procedures Terminology (CPT) and International Classification of Diseases, Ninth Revision (ICD-9) codes. The denominator population was defined as the total number of person-years (PYs) for all individuals in the database. Annual rates were computed overall and stratified by age, sex, and concomitant procedure. Results: There were 283,810 ACL reconstructions and 385,384,623 PYs from 2002 to 2014. The overall rate of ACL reconstruction increased 22%, from 61.4 per 100,000 PYs in 2002 to 74.6 per 100,000 PYs in 2014. Rates of isolated ACL reconstruction were relatively stable over the study period. However, among children and adolescents, rates of both isolated ACL reconstruction and ACL reconstruction with concomitant meniscal surgery increased substantially. Adolescents aged 13 to 17 years had the highest absolute rates of ACL reconstruction, and their rates increased dramatically over the 13-year study period (isolated, +37%; ACL + meniscal repair, +107%; ACL + meniscectomy, +63%). Rates of isolated ACL reconstruction were similar for males and females (26.1 vs 25.6 per 100,000 PYs, respectively, in 2014), but males had higher rates of ACL reconstruction with concomitant meniscal surgery than females. Conclusion: Incidence rates of isolated ACL reconstruction and rates of concomitant meniscal surgery have increased, particularly among children and adolescents. Clinical Relevance: A renewed focus on adoption of injury prevention programs is needed to mitigate these trends. In addition, more research is needed on long-term patient outcomes and postoperative health care utilization after ACL reconstruction, with a focus on understanding the sex-based disparity in concomitant meniscal surgery

Oral contraceptive use and anterior cruciate ligament injury: comparison of active comparator new user cohort and case-control study designs

Background: This study further investigates a protective association between oral contraceptive (OC) use and anterior cruciate ligament (ACL) injury noted in prior case-control studies. Methods: Active comparator new user cohort analysis of women aged 13–45 years in the United States from the IBM MarketScan Commercial Claims and Encounters database who newly-initiated low-dose OCs (exposed) or underwent intrauterine device (IUD) insertion (comparison group) from 2000 to 2014. Women were followed for ACL injury starting 90 days after OC initiation or IUD insertion until OC or IUD discontinuation or end of continuous enrollment. Adjusted hazard ratios (adjHR) and 95% confidence intervals (CI) were estimated controlling for age. Secondary analysis replicated previously-published case-control studies assessing “ever” versus “never” OC use over 1- and 5-year periods among women who underwent ACL reconstruction compared to age-matched controls. Results: In the cohort analysis, 2,370,286 women initiated OCs and 621,798 underwent IUD insertion. There were 3571 (0.15%) ACL injuries during an average 370.6 days of continuous OC use and 1620 (0.26%) during an average 590.5 days of IUD use. No difference in risk of ACL injury was observed between OC initiators and IUD users (adjHR = 0.95; 95%CI 0.89, 1.01). The case-control analysis replicated the slight protective association observed in prior studies over a 5-year period (OR = 0.90; 95%CI 0.85, 0.94). Conclusions: This cohort study suggests no association between OC use and ACL injury, while the case-control study suggested bias from uncontrolled confounding and selection factors may have influenced previous findings that suggested a protective association between OC use and ACL injury

Potential medication-related problems in older breast, colon, and lung cancer patients in the United States

Background: Older adults are often exposed to multiple medications, some of which could be inappropriate or have the potential to interact with each other. Older cancer patients may be at increased risk for medication-related problems due to exposure to cancer-directed treatment. Methods: We described patterns of potentially inappropriate medication (PIM) use and potential drug-chemotherapy interactions among adults age 66+ years diagnosed with stage I-III breast, stage II-III colon, and stage I to II lung cancer. Within the Surveillance, Epidemiology, and End Results-Medicare database, patients had to have Medicare Part D coverage with 1+ prescription in the diagnosis month and Medicare Parts A/B coverage in the prior 12 months. We estimated monthly prevalence of any and cancer-related PIM from 6 months pre- to 23 months post-cancer diagnosis and 12-month period prevalence of potential drug- chemotherapy interactions. Results: Overall, 19,318 breast, 7,283 colon, and 7,237 lung cancer patients were evaluated. Monthly PIM prevalence was stable prediagnosis (37%-40%), but increased in the year following a colon or lung cancer diagnosis, and decreased following a breast cancer diagnosis. Changes in PIM prevalence were driven primarily by cancer-related PIM in patients on chemotherapy. Potential drug-chemotherapy interactions were observed in all cohorts, with prevalent interactions involving hydrochlorothiazide, warfarin, and proton-pump inhibitors. Conclusions: There was a high burden of potential medication-related problems among older cancer patients; future research to evaluate outcomes of these exposures is warranted. Impact: Older adults diagnosed with cancer have unique medication management needs. Thus, pharmacy specialists should be integrated into multidisciplinary teams caring for these patients

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