Real-world opioid use among patients with migraine enrolled in US commercial insurance and risk factors associated with migraine progression.

BACKGROUND: Migraineurs may be categorized as having episodic migraine (EM: < 15 headache days/month) or chronic migraine (CM: ≥ 15 days/month for > 3 months with ≥ 8 days/month having features of migraine). Opioid use has been linked to progression from EM to CM. OBJECTIVE: To describe the utilization of opioid prescriptions among patients with migraine, to determine the association between opioid use and migraine progression, and to explore demographic and clinical risk factors for migraine progression. METHODS: This retrospective cohort study used Optum's deidentified Clinformatics Data Mart Database from January 2015 to December 2018. Adult patients with a migraine diagnosis and continuous health plan enrollment were included. Opioid use was measured by average daily morphine equivalent dose, also known as morphine milligram equivalent (MME). Descriptive statistics were used to summarize the opioid use by patient demographic and clinical characteristics. A Cox proportional hazards model with stepwise selection was used to determine the risk factors of new-onset CM. RESULTS: Overall, 35% of patients with migraine (27,331 of 78,134) received prescription opioids (> 0 MME/day) during the 12-month follow-up period. Higher opioid dosage was found in patients who had CM and comorbidities of interest. Compared with patients with EM, patients with CM were twice as likely to receive at least 20 MME/day (CM 3.8% vs EM 1.9%) and had a higher median opioid day supply (CM 20 vs EM 10) during follow-up. About 7% of patients with CM with at least 1 opioid prescription had at least 50 MME/day in any 90-day period during follow-up. A significant association was found between MME level and the likelihood of new-onset CM. Additional significant risk factors of migraine progression included younger age, female sex, South and West regions, and having a diagnosis of medication overuse headache, depression, back pain, or fibromyalgia (all P < 0.05). CONCLUSIONS: Despite guidelines and the availability of more migraine-specific treatments, opioids are still commonly prescribed to patients with migraines in real-world practice, especially for those with CM. In this study population, a higher risk of new-onset CM was associated with receiving higher opioid doses.

Healthcare utilization and costs among patients with chronic migraine, episodic migraine, and tension-type headache enrolled in commercial insurance plans.

OBJECTIVE: To quantify and compare healthcare utilization and costs for patients with chronic migraine (CM), episodic migraine (EM), and tension-type headache (TTH) enrolled in US commercial health plans. METHODS: This retrospective cohort study used the Optum Clinformatics® Data Mart database from January 2015 to December 2018. Adult patients with a diagnosis of EM, CM or TTH and at least 12 months of continuous enrollment before and after diagnosis were included. Inverse probability of treatment weighting was used to adjust for baseline differences among the three groups. Patient demographic and clinical characteristics at baseline, and healthcare utilization and costs during follow-up, were described and compared between the three groups. RESULTS: A total of 45,849 patients were included: 8955 with CM, 31,961 with EM, and 4933 with TTH. The total all-cause annual direct medical costs of patients with CM ($17,878) were 1.38 times higher (95% CI: 1.31-1.44) than those with EM ($12,986), and 2.26 times higher (95% CI: 2.08-2.47) than those with TTH ($7902). The annual migraine/TTH-related costs of patients with CM ($1869) were 4.19 times higher (95% CI: 3.92-4.48) than those with EM ($446), and 11.90 times (95% CI: 10.59-13.52) higher than those with TTH ($157). In the adjusted analyses, for all service categories (emergency department, inpatient, outpatient, and prescriptions), the expected costs in the migraine groups were higher than in the TTH group (all p < 0.001), while controlling for covariates. Main findings were consistent in both weighted and unweighted samples, and with both unadjusted and adjusted analyses. CONCLUSION: This study provides an updated assessment of healthcare utilization and expenditures for adult patients with primary headache disorders. Compared to TTH, migraine is associated with higher resource use and direct medical costs, especially for those with a chronic condition. Future studies are needed to understand the indirect medical costs (productivity loss) and humanistic burden (quality of life) between migraine and TTH.

Analysis of Suicide After Cancer Diagnosis by US County-Level Income and Rural vs Urban Designation, 2000-2016.

Importance: Studies suggest the risk of suicide among people with cancer diagnosis is higher compared with the general population. However, little is known about how suicide risk among people diagnosed with cancer might vary according to area-level income and rurality. Objective: To examine whether the risks and patterns of suicide mortality among people with a cancer diagnosis differ by US county-level median income and rural or urban status. Design, Setting, and Participants: A retrospective, population-based cohort study following up individuals who were diagnosed with cancer between January 1, 2000, and December 31, 2016, was conducted. The Surveillance, Epidemiology, and End Results Program 18 registries (SEER 18) database was used to obtain data on persons diagnosed with a first primary malignant tumor. Comparisons with the general US population were based on mortality data collected by the National Center for Health Statistics. Analyses were conducted from February 22 to October 14, 2020. Exposures: County-level median household income and urban or rural status. Main Outcomes and Measures: Standardized mortality ratios (SMRs) of suicide deaths and annual percentage changes (APCs) of SMRs. Results: The SEER 18 database included 5 362 782 persons with cancer diagnoses living in 635 counties. Most study participants were men (51.2%), White (72.2%), and older than 65 years (49.7%). Among them, 6357 persons died of suicide (SMR, 1.41; 95% CI, 1.38-1.44). People with cancer living in the lowest-income counties had a significantly higher risk (SMR, 1.94; 95% CI, 1.76-2.13) than those in the highest-income counties (SMR, 1.30; 95% CI, 1.26-1.34). Those living in rural counties also had significantly higher SMR than those in urban counties (SMR, 1.81; 95% CI, 1.70-1.92 vs SMR, 1.35; 95% CI, 1.32-1.39). For all county groups, the SMRs were the highest within the first year following cancer diagnosis. However, among people living in the lowest-income counties, the risk remained significantly high even after 10 or more years following cancer diagnosis (SMR, 1.83; 95% CI, 1.31-2.48). The comparative risk of suicide mortality within 1 year following cancer diagnosis significantly decreased over the years but then plateaued in the highest-income (2005-2015: APC, 2.03%; 95% CI, -0.97% to 5.13%), lowest-income (2010-2015: APC, 4.80%; 95% CI, -19.97% to 37.24%), and rural (2004-2015: APC, 1.83; 95% CI, -1.98% to 5.79%) counties. Conclusions and Relevance: This cohort study showed disparities in suicide risks and their patterns among people diagnosed with cancer by county-level income and rural or urban status. The findings suggest that additional research and effort to provide psychological services addressing these disparities among people with cancer may be beneficial.

Effect of multimodal information delivery for diabetes care on colorectal cancer screening uptake among individuals with type 2 diabetes.

Despite the significant increase in the risk of colorectal cancer (CRC), one-third of individuals with diabetes who met screening recommendations, reported not being up-to-date on CRC screening in the United States. We determined the means through which individuals with type 2 diabetes (T2DM) learned about diabetes care; we further examined their associations with CRC screening uptake. This was a retrospective study of US adults aged 50-75 years diagnosed with T2DM (sample n = 5595, representing 14,724,933 Americans). Data from the 2011-2014 Medical Expenditure Panel Survey were analyzed to compare CRC screening uptake in four learning groups for diabetes care: (1) did not learn, (2) learning from health providers only, (3) learning from other sources (including online sources and group class), and (4) learning from health providers and other sources together (combined learning group). Overall, 70.4% individuals with T2DM were up-to-date with CRC screening during 2011-2014. In multivariate logistic regression analysis, the combined learning group had 1.32 (95% confidence interval, 1.01-1.74) times higher odds of being up-to-date on CRC screening than those who did not learn about diabetes care. The odds of being up-to-date on CRC screening were not significant for other learning groups. Our findings suggest that combined ways of health information delivery for diabetes care is associated with increased odds of being up-to-date on CRC screening among individuals with T2DM. Multimodal health information delivery has the potential to result in unintended, positive consequences in preventive care services use.

Serious Adverse Drug Events Reported to the FDA: Analysis of the FDA Adverse Event Reporting System 2006-2014 Database.

BACKGROUND: Data on adverse drug events (ADEs) observed at the population level provide important evidence regarding the safety of a pharmaceutical product in real-world settings. Recent patterns in serious and fatal ADE reporting have not been documented. OBJECTIVE: To assess recent patterns in serious and fatal ADE reports in the United States. METHODS: We conducted a retrospective analysis of the publicly available 2006-2014 FDA Adverse Event Reporting System database. Non-U.S. reports, reports from clinical trials, and reports with missing outcome data were excluded. The annual numbers of ADEs with reported outcome of death, disability, and other serious outcomes were determined. Types (direct, manufacturer expedited, or manufacturer periodic) and sources (consumer, health professional, or other) of these serious ADE reports were also identified. The distribution of serious ADE reports by patient age groups (< 18, 18-44, 45-64, and ≥ 65 years) was determined. Drugs listed as primary suspects in serious ADEs (death, disability, and other serious outcomes) were identified and ranked. Descriptive statistics were used to characterize the patterns in serious or fatal ADE reporting. RESULTS: From 2006 to 2014, the number of serious ADEs reported to the FDA increased 2-fold. A total of 902,323 serious outcomes were reported over the 9-year study period: 244,408 deaths, 72,141 disabilities, and 585,774 other serious outcomes. The relative percentage of reports of deaths was highest during 2012 (32.4%). The percentage of reports of disability was highest during 2006 (12.1%). Overall, the "other serious outcomes" category accounted for almost 65% of serious ADEs reports. Expedited reports from drug manufacturers were most common (about 72%) of the serious ADEs with available data on report type. Health professionals (47.3%) were the most common source of report followed by consumers (36.1%) and other sources (16.6%). A disproportionately high number of reported ADEs was among patients aged 45-64 years (40%) and ≥ 65 years (32.6%). Antineoplastic drugs were more frequently reported with deaths. Three antidepressant drugs were among the top 10 drugs reported with disability. During 2006-2014, there were 38 drugs with more than 1,000 reports of serious ADEs in a given year: 2 drugs currently withdrawn from the market (rofecoxib and parecoxib), 10 drugs with an FDA risk evaluation and mitigation strategies (REMS) program, 13 biologic or specialty drugs, and 14 others. CONCLUSIONS: An overall increase in the trend of the number of serious ADE reports was observed from 2006 to 2014. Drugs with a REMS program and biologic and specialty drugs were involved in a significant number of reported serious ADEs. Data on reporting patterns can guide surveillance and pharmacoepidemiological studies to understand the public health burden of serious ADEs. DISCLOSURES: No outside funding supported this study. Hansen has received consulting fees from and has provided expert testimony for Daichii Sankyo and Takeda. The other authors have nothing to disclose.

Patterns of treatment modifications among newly treated hypertensive patients: does choice of modification strategy affect likelihood of treatment discontinuation?

OBJECTIVES: Treatment modifications--addition, uptitration, switching, and downtitration--are necessary to address issues such as unattained blood pressure goals, adverse drug events, drug cost, or patient dissatisfaction which lead to treatment discontinuation. This study assessed the patterns of treatment modifications, and compared the rates of treatment modification and time-to-treatment modification across five antihypertensive drug classes (ADCs). Additionally, the association between treatment modification strategies and the likelihood of treatment discontinuation was assessed. METHODS: This is a retrospective cohort study using the BlueCross-BlueShield of Texas commercial claims database (2008-2012). Treatment modifications that occurred within 1 year of starting hypertension treatment were identified. Patients who received treatment modifications were followed for 12 months to determine if and when they discontinued treatment. Cox regression models were used to determine the likelihood of treatment modification and treatment discontinuation. RESULTS: About 48.5% of patients received treatment modifications within 1 year of treatment initiation. Rates of treatment modification were significantly different across ADCs; angiotensin-converting enzyme inhibitor and angiotensin receptor blocker users were less likely to receive treatment modifications compared with other ADCs. Mean time-to-treatment modification was more than 100 days for adding and uptitrating, and more than 140 days for switching and downtitrating. Patients intensifying treatment by adding medications were about 25% (vs. uptitration) and 50% (vs. switching) less likely to discontinue treatment. CONCLUSION: Treatment modifications are common among newly treated hypertensive patients, and the rates vary significantly across ADCs. In the real world, treatment modifications occur much later than the 30-day timeline recommended by guidelines. Addition of drugs may be a preferred approach for intensifying treatment of patients at a high risk of treatment discontinuation.

Utilization patterns of antihypertensive drugs among the chronic kidney disease population in the United States: a cross-sectional analysis of the national health and nutrition examination survey.

PURPOSE: Antihypertensive drugs are prescribed to patients with chronic kidney disease (CKD) for their cardioprotective and renoprotective effects. Nationally representative information on the use of antihypertensive drugs among CKD patients is limited. The purpose of this study was to assess the utilization patterns of antihypertensive drugs among the CKD population (stages I-IV) in the United States. METHODS: We conducted a retrospective cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) panels from 2005-2006, 2007-2008, and 2009-2010. The estimated glomerular filtration rate was calculated and kidney damage was assessed to identify participants with CKD. The demographic and clinical characteristics of the participants with CKD were reported, as were the antihypertensive drugs they used. FINDINGS: A total weighted sample of 116,231,361 participants representative of the CKD population in the United States (stages I-IV) was identified. Less than one half of the participants with CKD in the NHANES were using antihypertensive drugs. ß-blockers were the most commonly used and angiotensin II receptor blockers were the least used antihypertensive agents among participants with CKD. Age (≥70 years), awareness of hypertension or diabetes, and higher stage of CKD were associated with an increased likelihood of antihypertensive drug use among participants with CKD. IMPLICATIONS: The results of our analyses suggest that antihypertensive drugs are underused in the CKD population, and the use of preferred agents (ie, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers) is low. Efforts should be directed toward emphasizing the importance of using antihypertensive drugs in the CKD population.

Vancomycin dosing in healthy-weight, overweight, and obese pediatric patients.

OBJECTIVES: With an increase in vancomycin resistance and the prevalence of obesity in children, alterations of vancomycin dosing regimens may be necessary to achieve target serum concentrations. The primary objective of this study was to describe initial vancomycin dosing with resulting serum concentrations in healthy-weight and overweight/obese children. Secondary objectives include comparing vancomycin dosing regimens of healthy-weight and overweight/obese patients that produced target trough serum concentrations and evaluating the likelihood of attaining target concentrations by patient characteristics. METHODS: This retrospective review evaluated healthy-weight and overweight/obese patients, aged 2 to 18 years, who had vancomycin trough serum concentrations obtained between 2005 and 2010. Vancomycin dosing, initial trough serum concentrations, pharmacokinetic parameters, and patient demographics were collected for analysis. Target trough serum concentrations were defined as 10 to 20 mg/L. RESULTS: The study included 98 patients (48 healthy weight, 50 overweight/obese) of which only 14 patients (14.2%, 6 healthy weight, 8 obese) reached a target trough serum concentration with empiric dosing. No difference was found between the mean daily dosing of vancomycin that produced target trough serum concentrations in healthy-weight or overweight/obese patients (53.63 mg/kg/day vs 51.6 mg/kg/day, respectively). Demographic or clinical characteristics were not found to be associated with the likelihood of target trough serum concentration attainment. CONCLUSIONS: Vancomycin dosing in healthy-weight and overweight/obese pediatric patients did not reach target trough serum concentrations most of the time. In obtaining initial target serum concentrations, no dosing difference was identified for overweight/obese patients compared with healthy-weight patients. Alternate dosing strategies, therapeutic monitoring, and clinical outcomes should continue to be evaluated in this population.