Risk of Suicidal Ideation and Behavior Following Early-Onset Idiopathic Restless Legs Syndrome Treatment.

PURPOSE: To estimate incidence rates of suicidal ideation and behavior following treatment initiation with gabapentinoids or dopamine agonists (DAs) in patients with newly diagnosed early-onset idiopathic restless legs syndrome (RLS) and to examine suicidal behavior risk, comparing between those receiving gabapentinoids and DAs. METHODS: A new user retrospective cohort study using MarketScan claims data from 2012 to 2019 was conducted. Exposures were monotherapy gabapentinoids or DAs initiated within 60 days of new RLS diagnosis. Three varying outcome measures of suicidality were examined and incidence rates were calculated for each. A log-binomial regression model the estimated relative risk (RR) of the outcomes with gabapentinoids. Propensity score weighting adjusted for baseline covariates, including age, substance use disorders, hyperlipidemia, antipsychotic use, hypnotic/sedative use, and mood stabilizer use, which were most imbalanced before weighting. RESULTS: The cohort included 6672 patients, with 4986 (74.7%) initiating a DA and 1686 (25.3%) initiating a gabapentinoid. Incidence rates for all outcome measures were higher in the gabapentinoid group (suicidality: 21.6 vs. 10.7 per 1000 person-years; suicidality with self-harm: 23.0 vs. 11.1 per 1000 person-years; overdose- and suicide-related events: 30.0 vs. 15.5 person-years). Associated risk of suicidality (adjusted RR, 1.27 [95% CI, 0.86-1.88]); suicidality with self-harm (adjusted RR, 1.30 [95% CI, 0.89-1.90]); or overdose- and suicide-related events (adjusted RR, 1.30 [95% CI, 0.93-1.80]) was not significant with gabapentinoids. CONCLUSIONS: Incidence rates for suicidal ideation and behavior were higher among the gabapentinoid group, although increased risk was not detected after adjustment. A possible signal cannot be ruled out given limitations of the data and rarity of the outcome.

High-throughput screening for prescribing cascades among real world statin initiators.

PURPOSE: Statins are among the most prevalent medications prescribed and associated with adverse events that may prompt additional treatment (i.e., a prescribing cascade). No comprehensive assessment of statin-related prescribing cascades has been performed to our knowledge. METHODS: We utilized sequence symmetry analysis to iteratively screen prescribing sequences of all therapeutic classes ("marker" classes) based on Level 4 Anatomical Therapeutic Chemical codes among adult statin initiators, using IBM Marketscan commercial and Medicare supplemental claims databases (2005-2019). Order of initiation and secular trend-adjusted sequence ratios were calculated for each statin-marker class dyad, among marker class initiators ±90 days of statin initiation. Among signals classified as prescribing cascades, we calculated naturalistic number needed to harm (NNTH) within 1 year as the inverse of the excess risk among exposed. RESULTS: We identified 2 265 519 statin initiators (mean ± SD age, 56.4 ± 12.0 years; 48.7% women; 7.5% with cardiovascular disease). Simvastatin (34.4% of statin initiators) and atorvastatin (33.9%) were the most commonly initiated statins. We identified 160 significant statin-marker class dyad signals, of which 35.6% (n = 57) were classified as potential prescribing cascades. Of the top 25 strongest signals (lowest NNTH), 12 were classified as potential prescribing cascades, including osmotically acting laxatives (NNTH, 44, 95% CI 43-46), opioids + non-opioid combination analgesics (81, 95% CI 74-91), and first-generation cephalosporins (204, 95% CI 175-246). CONCLUSIONS: Using high-throughput sequence symmetry analysis screening, we identified previously known prescribing cascades as well as potentially new prescribing cascades based on known and unknown statin-related adverse events.

Concomitant use of levothyroxine and interacting medications in U.S. ambulatory care visits.

BACKGROUND: Levothyroxine (LT4) is the third most commonly prescribed medication in the United States. It is a narrow therapeutic index medication, and thus can be impacted by drug-drug interactions, which are primarily available over-the-counter. The prevalence and associated factors with concomitant interacting drugs with LT4 is limited since over-the-counter products are not routinely captured in many drug databases. OBJECTIVE: This study aimed to characterize the concomitant use of LT4 with interacting drugs at ambulatory care visits in the United States. DESIGN: A cross-sectional analysis of the National Ambulatory Medical Care Survey (NAMCS) from 2006 to 2018 was completed. SETTING AND PARTICIPANTS: Ambulatory care visits in the United States involving adult patients with a LT4 prescription were included in the analysis. OUTCOME MEASURES: The primary outcome was initiation or continuation of a selected concomitant interacting drug which impacts LT4 absorption (e.g., proton pump inhibitor) in a patient visit in conjunction with LT4. RESULTS: The authors analyzed 372,942,000 visits (weighted from a sample of 14,880) with a reported LT4 prescription. Concomitant use of interacting drugs with LT4 occurred in 24.4% of visits in which 80% of interacting drugs were proton pump inhibitors. Ages 35-49 years (adjusted odds ratio [aOR], 1.59), 50-64 years (aOR, 2.27), and ≥65 years (aOR, 2.87) compared to 18-34 years, female (aOR 1.37) versus males, and visits in 2014 or later (aOR, 1.27) versus 2006-2009 were associated with increased odds of concomitant interacting drug use in multivariable analysis. CONCLUSION: At ambulatory care visits between 2006 and 2018, concomitant use of LT4 and interacting drugs impacted one-quarter of patient visits. Increased age, females, and visits later in the study period were associated with increased odds for concomitant interacting drugs. Additional work is needed to identify downstream consequences of concomitant use.

Prescription Patterns of Adjuvant Pain Medications Following an Opioid Supply Restriction Law: An Interrupted Time Series Analysis.

BACKGROUND: Florida House Bill 21 (HB21) was implemented in July 2018 to limit prescriptions of Schedule II opioids for acute pain patients, but it is unclear whether such restrictions have a collateral influence on the utilization of commonly prescribed adjuvant pain medications. OBJECTIVE: The objective of this study was to assess whether this law was associated with a change in use patterns of gabapentinoids, benzodiazepines, and muscle relaxants. METHODS: We obtained prescription claims for medications dispensed from January 1, 2015, to June 31, 2019, from a health plan serving a large Florida employer. Interrupted time series analyses were conducted to compare pre-HB21 and post-HB21 implementation changes in the mean monthly number of users and prescriptions for gabapentinoids, benzodiazepines, and muscle relaxants. RESULTS: There was a 6% immediate increase (relative risk: 1.06; 95% confidence interval: 1.02, 1.11) in the monthly proportion of gabapentinoid users, and an 11% immediate increase in the monthly proportion of gabapentinoids prescriptions (relative risk: 1.11; 95% confidence interval: 1.04, 1.18) per 1000 patients following law implementation. However, after the law, we observed a significant reduction in trend for the monthly proportion of muscle relaxants and benzodiazepine users. CONCLUSIONS: An increased number of patients and prescriptions were observed for gabapentinoids, while fewer patients received benzodiazepines and muscle relaxants after HB21. In previous studies, opioid prescription restriction laws are shown to reduce opioids, but this work suggests that these laws may also have unintended consequences for the use of adjunctive medications that were not intended to be affected.

Changes in Prescribing by Provider Type Following a State Prescription Opioid Restriction Law.

BACKGROUND: Many states have implemented opioid days' supply restriction policies, leading to reductions in opioid prescribing. Although research within certain provider types exist, no study has evaluated a restriction policy by various provider types. OBJECTIVE: To evaluate changes in opioid utilization following a days' supply restriction policy stratified by provider type: surgery, emergency medicine, primary care, specialty care, and dentistry. DESIGN: Interrupted time series (ITS) PARTICIPANTS: Opioid prescription claims of patients in a private health plan serving a large Florida employer from 1/1/2015 to 3/31/2019. Provider types were determined using the Healthcare Provider Taxonomy Code associated with the national provider identifier (NPI). INTERVENTIONS: Florida's opioid restriction policy implemented on July 1, 2018. MAIN MEASURES: Changes in mean morphine milligram equivalent (MMEs), mean days' supply, and mean number of units dispensed per opioid prescription before and after policy implementation. KEY RESULTS: There were 10,583 opioid initial prescriptions dispensed. Treating providers were classified as surgery (16.4%; n = 1732), emergency care (14.3%; n = 1516), primary care (21.2%; n = 2241), specialty care (11.4%; n = 1207), and dentistry providers (23.7%; n = 2511). Significant reductions in mean days' supply were observed across most provider types ranging from 14% reduction for dentistry providers to 41% reduction for specialty care providers. Significant changes were observed for emergency care and specialty care providers with a 30% (p = 0.001)and 29% (p < 0.001) reduction in mean MME, respectively, and a 27% (p = 0.040) reduction in mean number of units dispensed in emergency care providers, after implementation. Pre-implementation trends in opioid prescribing varied by provider type impacting the effects of the opioid days' supply restriction policy. CONCLUSIONS: Pre-policy opioid prescribing varied by provider type with a differential impact on mean MMEs, mean days' supply, and mean number of units dispensed per prescription following implementation.

Evaluation of the key prescription sequence symmetry analysis assumption using the calcium channel blocker: Loop diuretic prescribing cascade.

OBJECTIVES: To evaluate the prescription sequence symmetry analysis assumption regarding balance between marker drug (i.e., medication used to treat a drug-induced adverse event) initiation rates before and after initiation of an index drug (i.e., medication that is potentially associated with the drug-induced adverse event) in the absence of prescribing cascades, we used a well-described example of loop diuretic initiation to treat dihydropyridine calcium channel blockers (DH CCB)-induced edema. STUDY DESIGN AND SETTING: The University of Florida Health Integrated Data Repository from June 2011 and July 2018 was used to assess temporal prescribing of DH CCB and loop diuretics within the prescription sequence symmetry analysis framework. Validation of the prescribing cascade was performed via clinical expert chart review. RESULTS: Among patients without heart failure who were initiated on DH CCB, 26 and 64 loop diuretics initiators started within 360 days before versus after DH CCB initiation, respectively, resulting in an adjusted sequence ratio (aSR) of 2.27 (95% CI, 1.44-3.58). Overall, 35 (54.7%) patients were determined to have a prescribing cascade. Removing patients who experienced a prescribing cascade resulted in an aSR of 1.05, 95% CI 0.62-1.78). CONCLUSION: Loop diuretic initiation rates before and after DH CCB initiation for reasons other a prescribing cascade were similar, thus confirming the prescription sequence symmetry analysis assumption.

Twelve-year trends in pharmacologic treatment of type 2 diabetes among patients with heart failure in the United States.

We conducted a cross-sectional analysis using a database from commercial health plans in the United States to describe trends in the use of antidiabetic medications among patients with type 2 diabetes and heart failure (HF) from 2006 through 2017. We used loop diuretic dose as a surrogate for HF severity (mild HF 0-40 mg/day, moderate-severe HF >40 mg/day). We assessed antidiabetic medication dispensing in the 90 days following HF diagnosis. Over the 12-year period, we identified an increase in the use of metformin (39.2% vs. 62.6%), dipeptidyl peptidase-4 inhibitors (DPP-4i) (0.5% vs. 17.1%) and sodium-glucose co-transporter-2 inhibitors (SGLT-2i) (0.0% vs. 9.0%), but a decrease in the use of sulphonylureas (47.8% vs. 27.8%) and thiazolidinediones (TZDs) (31.7% vs. 5.3%). In 2017, patients with moderate-severe HF more commonly used insulin (43.1%); a majority of mild HF patients used metformin (62.8%). A proportion of patients with moderate-severe HF used TZDs (4.4%). Among patients with diabetes and HF, the use of metformin and DPP-4i rapidly increased, but a proportion of patients with moderate-severe HF continued to use TZDs. Despite their promising cardiovascular safety profile, SGLT-2i use remains limited.

Trends and Components of Thyroid Status Evaluation in Commercially Insured Adults in the United States, 2006-2020.

CONTEXT: Thyroid-stimulating hormone (TSH) is one of the most ordered laboratory tests. OBJECTIVE: Determine trends of TSH testing rates and components of thyroid function testing. METHODS: This was a retrospective analysis of adults 18-64 years old without evidence of thyroid disease with at least 365 days of continuous enrollment between 2006 and 2020 in the IBM MarketScan Claims Database. The main outcome measures were trends of TSH tests/1000 eligible patient-months stratified by age, sex, and region and composition of thyroid function testing. RESULTS: Among 67 353 280 patients meeting eligibility criteria, we identified 25 606 518 TSH tests and 15 138 211 patients with ≥1 TSH test. Patients contributing an episode of TSH testing were most commonly 45-54 years old (29.8%) and female (63.6%). TSH testing rates remained consistent throughout the study period with 11.4 and 11.7 TSH tests/1000 person-months in the first and last study months, respectively (mean 12.2 TSH tests/1000 person-months). TSH testing rates dropped sharply in the spring of 2020 (4.2 TSH tests/1000 person-months). Females showed a nearly 2-fold higher rate of TSH testing than males (16.1 TSH tests/1000 person-months vs 8.6 TSH tests/1000 person-months). TSH testing rates increased with age (8.2 TSH tests/1000 person-months among individuals 18-34 years old vs 15.4 TSH tests/1000 person-months among individuals 55-64 years old). No difference in TSH testing rates was noted between regions. Thyroid function testing episodes included only TSH in most cases (70.8%). CONCLUSION: TSH testing rates among commercially insured individuals without known thyroid disease appears stable over time, with higher frequency in females and with increasing age.

Evaluating Provider and Pharmacy Discordance in Potential Calcium Channel Blocker-Loop Diuretic Prescribing Cascade.

BACKGROUND: Prescribing cascades occur when a drug-induced adverse event is treated with a new medication. Identifying clinical scenarios in which prescribing cascades are more likely to occur may help determine ways to prevent prescribing cascades. OBJECTIVE: To understand the extent to which discordant providers and discordant pharmacies contribute to the dihydropyridine calcium channel blocker (DH CCB)-loop diuretic prescribing cascade. STUDY POPULATION AND DESIGN: A retrospective cohort study using Medicare Fee-For-Service data (2011-2018) of adults aged ≥ 66 years. EXPOSURES: Patients who initiated DH CCB with subsequent initiation of loop diuretic (DH CCB-loop diuretic dyad) within 90 days or patients who initiated angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) with subsequent initiation of a loop diuretic (ACEI/ARB-loop diuretic dyad; control). MAIN OUTCOMES: The primary outcomes were provider and pharmacy discordance for prescribing cascades and control drug pairs. Baseline clinical and socio-demographic characteristics were balanced using inverse probability of treatment weighting with propensity scores. RESULTS:  Overall, we identified 1987 DH CCB-loop diuretic dyads and 3148 ACEI/ARB-loop diuretic dyads. Discordant providers occurred in 64% of DH CCB-loop diuretic dyads and 55% of ACEI/ARB-loop diuretic dyads, while discordant pharmacies occurred in 19% of DH CCB-loop diuretic dyads and 16% of ACEI/ARB-loop diuretic dyads. After adjustment, the risk of having discordant providers was 20% {Relative Risk (RR) 1.20 [95% confidence interval (CI), 1.14-1.26]} higher in the DH CCB-loop diuretic dyad compared with the ACEI/ARB-loop diuretic dyad. Moreover, pharmacy discordance was 17% (RR 1.17 [95% CI 1.02-1.33]) higher. CONCLUSION: Our findings suggest that discordant providers and discordant pharmacies were more commonly involved in the potential prescribing cascade when compared with a similar control dyad of medications. Opportunities for enhanced care coordination and medication reconciliation should be explored to prevent unnecessary polypharmacy.

Trends in the appropriateness of oral antibiotic prescriptions dispensed in the United States from 2010 to 2018.

BACKGROUND: One of the goals established by the United States National Action Plan to Combat Antibiotic-Resistant Bacteria is to reduce inappropriate outpatient antibiotic prescriptions by 50% by 2020. Recent data on the achievement of this goal is lacking. The objective of our study was to examine recent trends in the appropriateness of oral antibiotic prescriptions dispensed to a commercially insured population in outpatient settings in the United States to quantify the relative trend in inappropriate antibiotic prescribing from 2010 to 2018. METHODS: Our cross-sectional analysis examined oral antibiotic prescriptions dispensed in outpatient settings using the IBM MarketScan Commercial Data from January 2010 to December 2018. Trends in the annual proportion of antibiotic prescriptions classified as appropriate, potentially appropriate, inappropriate, or without any medical visit during a 7 days look-back period were estimated using multivariable generalized linear models with Poisson distribution adjusting for beneficiaries' demographic and infectious conditions. RESULTS: Approximately 170 million oral antibiotic prescriptions were dispensed to 86 million beneficiaries during 2010 to 2018. The mean age of the study population was 34.5 (±19.1) years, with 58.4% females and 24.6% children. We observed a 12.9% (95% Confidence Interval [CI] = 12.6%-13.2%; p < 0.01) decline in rates of antibiotic use, from 832 to 727 prescriptions per 1000 beneficiaries, from 2010 to 2018. The proportion of prescriptions classified as appropriate increased by 36.7% (95% CI = 36.4%-36.9%; p < 0.01); potentially appropriate prescriptions increased by 9.3% (95% CI = 9.1%-9.4%; p < 0.01); whereas inappropriate prescriptions and those without a medical visit declined by 11.3% (95% CI = 11.2%-11.4%; p < 0.01) and 14.0% (95% CI = 13.9%-14.2%; p < 0.01), respectively. Similar declining trends were observed in use and proportion of inappropriate prescriptions for broad-spectrum antibiotics. In 2018, amoxicillin and azithromycin were the most common appropriate and inappropriate prescription fills, respectively. CONCLUSION: Although antibiotic use and inappropriate prescribing declined steadily from 2010 to 2018 in the United States, this study demonstrates that we have not achieved the national goal of reducing inappropriate antibiotic prescribing by 50%.

Rapid recognition and optimal management of hemophilia in the emergency department: A quality improvement project.

Objectives: This study aimed to assess the effectiveness of a continuous quality improvement initiative at the University of Florida Health Physicians practice in reducing the time to administer factor replacement therapy (FRT) for hemophilia patients presenting with bleeding in the emergency department (ED). Methods: The study, a quasi-experimental, interventional design, was conducted between January 2020 and January 2023. The intervention, implemented in September 2021, involved training ED physicians, creating a specialized medication order set within the electronic health record (EHR), and a rapid triage system. The effectiveness was measured by comparing the time from ED arrival to factor administration before and after the intervention and benchmarking it against the National Bleeding Disorders Foundation's Medical and Scientific Advisory Council (MASAC)-recommended 1-hour timeline for factor administration. An interrupted time series (ITS) analysis with a generalized least squares model assessed the intervention's impact. Results: A total of 43 ED visits (22 pre-intervention and 21 post-intervention) were recorded. Post-intervention, the average time from ED arrival to factor administration decreased from 5.63 to 3.15 hours. There was no significant increase (27% vs. 29%) in the patients receiving factor within 1-hour of ED arrival. The ITS analysis predicted a 20-hour reduction in the average quarterly time to administer factor by the end of the study, an 84% decrease. Conclusions: The quality improvement program decreased the time to administer FRT for patients with hemophilia in the ED. However, the majority of patients did not achieve the 1-hour MASAC-recommended timeline for factor administration after ED arrival.

Pragmatic Model and Faculty Toolkit for PharmD Student Engagement in Social and Administrative Pharmacy Research.

OBJECTIVE: We aim to describe the development of a pharmacy student workgroup as an experiential education model to provide social and administrative pharmacy research opportunities and provide a toolkit for faculty seeking to increase student research engagement via this model. METHODS: Three pharmacy faculty with diverse training backgrounds but a common interest in opioid medications established a workgroup named the Opioid Research Workgroup. The workgroup consisted of first-year pharmacy students, research interns, and advanced graduate trainees. A hierarchical leadership model of supervision was implemented, whereby students reported progress on research tasks directly to an advanced graduate trainee leading a project team. To understand students' perspectives on the research experience and educational outcomes, students were asked to complete an anonymous voluntary survey after a year of participation. RESULTS: Since its establishment, the workgroup has published multiple conference abstracts, manuscripts, and grants. Students' overall satisfaction with the Workgroup on a scale of 1-5, 5 being very high, was 4.69. The successful scalability and longevity of this model are dependent on administrative support that protects faculty resources. The toolkit provided offers resources for those interested in adapting this model. CONCLUSION: Our experience with the pragmatic model of pharmacy student engagement in research proved successful in terms of research output and student training experience. Although the model can be applied across a variety of health science clinical and research topics, and faculty can leverage this approach to increase productivity in research output, faculty must ensure that resources are available to support this effort.

Comparative effectiveness of pegfilgrastim biosimilars vs originator for prevention of febrile neutropenia: A retrospective cohort study.

BACKGROUND: Real-world evidence on the comparative effectiveness of pegfilgrastim biosimilars compared with the originator product is limited. OBJECTIVE: To compare the risk of febrile neutropenia (FN) among users of pegfilgrastim biosimilars (pegfilgrastim-jmdb and pegfilgrastim-cbqv) and the originator product. METHODS: A retrospective cohort study was conducted using 2019 IBM MarketScan databases to assess comparative effectiveness of pegfilgrastim originator and biosimilars for prevention of FN among patients receiving myelosuppressive chemotherapy. Patients with cancer, including breast, lung, colorectal, esophageal and gastric, pancreatic, prostate, ovarian, and non-Hodgkin lymphomas, initiating myelosuppressive chemotherapy courses were selected. We further selected patients who used pegfilgrastim originator and biosimilars within 3 days of chemotherapy completion. FN-associated hospitalizations were measured by International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes. After 1:1 propensity score matching, we used equivalence (with a margin of 6%) hypothesis tests to compare FN-related hospitalization risk in the first cycle and across all cycles between biosimilars and originator users. RESULTS: A total of 2,045 patients were included, of which 445 (21.8%) used pegfilgrastim-jmdb, 636 (31.1%) used pegfilgrastim-cbqv, and 964 (47.1%) used pegfilgrastim originator. After matching, 13 out of 445 originator users and 17 out of 445 pegfilgrastim-jmdb users developed FN after the first chemotherapy cycle (risk difference was 0.9%; P < 0.001 for equivalence test indicating statistical equivalence). After matching, 14 out of 633 originator users and 16 out of 633 pegfilgrastim-cbqv users developed FN (risk difference was 0.32%; P < 0.001 for equivalence test indicating statistical equivalence). Results across all cycles (including the first cycle) were consistent with that in the first cycle. CONCLUSIONS: In this real-world study of patients with cancer receiving myelosuppressive chemotherapy, there was no difference in FN risk between patients receiving pegfilgrastim originator and biosimilars in the first cycle and across all cycles. These results add further to the current evidence on pegfilgrastim biosimilars and support wider adoption of pegfilgrastim biosimilars among payers, providers, and patients. Future studies assessing the tolerability, side effects, and other safety issues of pegfilgrastim biosimilars are needed.

Enhancing active learning of medication errors in the PharmD curriculum through a multi-perspective video-based experience.

INTRODUCTION: We created and assessed an immersive instructional series of video-based activities for pharmacy student evaluation of medication errors via root cause analysis (RCA). METHODS: A novel series of video vignettes showed a medication error from the perspectives of each healthcare team member involved. Students were engaged in a series of activities to guide them through RCA interspersed with the vignettes. A pre/post-assessment tool measured student-perceived skills and attitudes in medication error prevention and handling. Per item pre/post-mean scores were compared using Mann-Whitney U tests with Bonferroni correction. RESULTS: From N = 270 students, 231 and 163 completed the anonymous pre- and post-assessment, respectively. Most students positively endorsed attitude items at both assessment intervals, with no significant changes in mean for "learning how to improve patient safety is an appropriate use of time in pharmacy school" (pre-assessment = 4.26; post-assessment = 4.23). However, there were significant improvements in the skills items "I am confident in my ability to analyze a case to find the root causes of an error" (pre = 3.44; post = 3.85) and "I can identify the key factors in systems and processes that could lead to a medication error" (pre = 3.55; post = 3.88). CONCLUSIONS: Pharmacy students reported significantly improved self-perceived skills in handling and preventing medication errors, but not in attitudes, following the immersive instructional activity. There are opportunities to expand such an immersive instructional series in an interprofessional setting, which may yield different findings.

Oral fluoroquinolones and risk of aortic aneurysm or dissection: A nationwide population-based propensity score-matched cohort study.

STUDY OBJECTIVE: To investigate risk of aortic aneurysm or dissection in patients using oral fluoroquinolones compared to those using macrolides in real-world clinical practice among a large US general population. DESIGN: Retrospective cohort study design. DATA SOURCE: MarketScan commercial and Medicare supplemental databases. PATIENTS: Adults patients with at least one prescription fill for fluoroquinolone or macrolide antibiotics. INTERVENTION: Fluoroquinolone or macrolide antibiotics. MEASUREMENTS AND MAIN RESULTS: The primary outcome was estimated incidence of aortic aneurysm or dissection associated with the use of fluoroquinolones compared with macrolides during a 60-day follow-up period in a 1:1 propensity score-matched cohort. We identified 3,174,620 patients (1,587,310 in each group) after 1:1 propensity score matching. Crude incidence of aortic aneurysm or dissection was 1.9 cases per 1000 person-years among fluoroquinolone users and 1.2 cases per 1000 person-years among macrolide users. In multivariable Cox regression, compared with macrolides, the use of fluoroquinolones was associated with an increased risk of aortic aneurysm or dissection (aHR: 1.34; 95% CI: 1.17-1.54). The association was primarily driven by a high incidence of aortic aneurysm cases (95.8%). Results of sensitivity (e.g., fluoroquinolone exposure ranging from 7 to 14 days (aHR: 1.47; 95% CI: 1.26-1.71)) and subgroup analyses (e.g., ciprofloxacin (aHR: 1.26; 95% CI: 1.07-1.49) and levofloxacin (aHR: 1.44; 95% CI: 1.19-1.52)) remained consistent with main findings. CONCLUSIONS: Fluoroquinolone use was associated with a 34% increased risk of aortic aneurysm or dissection compared with macrolide use among a general US population.

Incident mental health episodes after initiation of gabapentinoids vs. dopamine agonists for early-onset idiopathic restless legs syndrome.

Limited long-term safety information exists for gabapentinoid treatment of idiopathic restless legs syndrome (RLS). We estimated incident mental health-related emergency department visits and hospitalizations with a primary mental health diagnosis (primary outcome) among early-onset idiopathic RLS patients following first-line treatment initiation and examined outcome risk with gabapentinoids compared with dopamine agonists (DAs). A retrospective cohort study was conducted using administrative claims data from 2012 to 2019. Adults with early-onset (18-44 years) idiopathic RLS initiating either gabapentinoids or DAs within 60 days of new diagnosis were followed up to two years. Incidence rates were calculated and a log-binomial regression model with propensity score weighting estimated relative risk of the outcome and of substance use disorders (SUDs) as a secondary analysis with gabapentinoids. Among a cohort of 6,672 patients, 4,986 (74.7%) initiated DAs and 1,686 (25.3%) gabapentinoids. Incidence of the primary outcome (49.8 [95% CI 40.8-69.3] per 1,000 person-years) and SUDs (49.5 [95% CI 40.6-59.9] per 1,000 person-years) were higher in the gabapentinoid group compared with the DA group. A statistically significant risk of mental health diagnoses with gabapentinoids was not detected, but SUD risk was significant after covariate adjustment. High-risk mental health comorbidities (i.e., SUDs) should be considered when initiating RLS treatments.

Continued potassium supplementation use following loop diuretic discontinuation in older adults: An evaluation of a prescribing cascade relic.

BACKGROUND: The use of a new medication (e.g., potassium supplementation) for managing a drug-induced adverse event (e.g., loop diuretic-induced hypokalemia) constitutes a prescribing cascade. However, loop diuretics are often stopped while potassium may be unnecessarily continued (i.e., relic). We aimed to quantify the occurrence of relics using older adults previously experiencing a loop diuretic-potassium prescribing cascade as an example. METHODS: We conducted a prescription sequence symmetry analysis using the population-based Medicare Fee-For-Service data (2011-2018) and partitioned the 150 days following potassium initiation by day to assess the daily treatment scenarios (i.e., loop diuretics alone, potassium alone, combination of loop diuretics and potassium, or neither). We calculated the proportion of patients developing the relic, proportion of person-days under potassium alone, the daily probability of the relic, and the proportion of patients filling potassium after loop diuretic discontinuation. We also identified the risk factors of the relic. RESULTS: We identified 284,369 loop diuretic initiators who were 8 times more likely to receive potassium supplementation simultaneously or after (i.e., the prescribing cascade), rather than before, loop diuretic initiation (aSR 8.0, 95% CI 7.9-8.2). Among the 66,451 loop diuretic initiators who subsequently (≤30 days) initiated potassium, 20,445 (30.8%) patients remained on potassium after loop diuretic discontinuation, and 9365 (14.1%) patients subsequently filled another potassium supplementation. Following loop diuretic initiation, 4.0% of person-days were for potassium alone, and daily probability of the relic was the highest after day 90 of loop diuretic initiation (5.6%). Older age, female sex, higher diuretic daily dose, and greater baseline comorbidities were risk factors for the relic, while patients having the same prescriber or pharmacy involved in the use of both medications were less likely to experience the relic. CONCLUSIONS: Our findings suggest the need for clinicians to be aware of the potential of relic to avoid unnecessary drug use.

Modifiable statin characteristics associated with potential statin-related prescribing cascades.

STUDY OBJECTIVE: Clinicians may prescribe new medications (marker drug) to treat statin-related (index drug) adverse events, constituting a prescribing cascade. We aimed to identify modifiable statin characteristics (intensity and individual statin agents) associated with lower risk of prescribing cascades to inform clinical decisions in the presence of statin-related adverse events. DESIGN: A secondary analysis based on our previous work, a high-throughput sequence symmetry analysis screening for potential statin-related prescribing cascades. DATA SOURCE: MarketScan Commercial and Medicare Supplemental Insurance claims databases between 2005 and 2019. PATIENTS: Adults who initiated a statin between 2007 and 2018, and who were continuously enrolled in the same healthcare plan for at least 720 days before and 360 days after statin initiation. INTERVENTION: Among the previously identified 57 potential prescribing cascades, 42 statin-marker class dyad with a sample size of ≥ 500 were assessed in this study. MEASUREMENTS: We measured patients' baseline characteristics within -360 days of statin initiation and reported by modifiable statin characteristics. We also performed logistic regression and reported the adjusted odds ratios (aOR) with 95% confidence intervals (CI) of modifiable statin characteristics after adjusting for baseline characteristics. MAIN RESULTS: We identified 1,307,867 statin initiators who met the study criteria (21% elderly, 52% female). Compared with patients initiating low-intensity statins, those initiating moderate- or high-intensity statins had significantly greater odds to develop 29 (69%) prescribing cascades, including antidiabetic drugs such as dipeptidyl peptidase 4 (DPP-4) inhibitors (aOR 1.22; 95% CI, 1.11-1.35) and glucagon-like peptide-1 (GLP-1) analogs (aOR 1.31; 95% CI, 1.16-1.47), and opioids (aOR 1.18; 95% CI, 1.13-1.23). Individual statin agent selection also had a differential effect on 34 (81%) of the prescribing cascades. For example, compared with simvastatin initiators, the probability of initiating osmotically acting laxatives was significantly higher for lovastatin initiators (aOR 1.09; 95% CI, 1.03-1.15) and significantly lower in atorvastatin initiators (aOR 0.92; 95% CI, 0.89-0.94). CONCLUSION: Compared with low-intensity statins, high-intensity statins are associated with increased risk in many potential prescribing cascades, while the choice of individual statin agents affects the risk of prescribing cascades bidirectionally.

Loop diuretic use following fluid resuscitation in the critically ill.

PURPOSE: To identify the incidence of continuation of newly initiated loop diuretics upon intensive care unit (ICU) and hospital discharge and identify factors associated with continuation. METHODS: This was a single-center retrospective study using electronic health records in the setting of adult ICUs at a quaternary care academic medical center. It involved patients with sepsis admitted to the ICU from January 1, 2014, to June 30, 2019, who received intravenous fluid resuscitation. The endpoints of interest were (1) the incidence of loop diuretic use during an ICU stay following fluid resuscitation, (2) continuation of loop diuretics following transition of care, and (3) potential factors associated with loop diuretic continuation after transition from the ICU. RESULTS: Of 3,591 patients who received intravenous fluid resuscitation for sepsis, 39.4% (n = 1,415) were newly started on loop diuretics during their ICU stay. Among patients who transitioned to the hospital ward from the ICU, loop diuretics were continued in 33% (388/1,193) of patients. At hospital discharge, 13.4% (52/388) of these patients were prescribed a loop diuretic to be used in the outpatient setting. History of liver disease, development of acute kidney injury, being on vasopressors while in the ICU, receiving blood products, and receiving greater than 90 mL/kg of bolus fluids were significant potential factors associated with loop diuretic continuation after transition from the ICU. CONCLUSION: New initiation of loop diuretics following intravenous fluid resuscitation in patients with sepsis during an ICU stay is a common occurrence. Studies are needed to assess the effect of this practice on patient outcomes and resource utilization.

Patient out-of-pocket and payer costs for pegfilgrastim originator vs biosimilars as primary prophylaxis of febrile neutropenia in the first cycle among a commercially insured population.

BACKGROUND: It is unknown whether using pegfilgrastim biosimilars is cost saving in a real-world setting. OBJECTIVE: To compare medical costs including pegfilgrastim drug costs and febrile neutropenia (FN) treatment and management costs between pegfilgrastim biosimilars (pegfilgrastim-jmdb, pegfilgrastim-cbqv) and originator users for primary prophylaxis of febrile neutropenia. METHODS: A retrospective cohort study using 2019 IBM MarketScan Commercial and Medicare Supplemental databases was conducted in adult patients with cancer initiating myelosuppressive chemotherapy courses. At least 2 diagnoses of the same cancer (at least 7 days apart) were required within 30 days of the chemotherapy initiation date. Pegfilgrastim (excluding on-body injector) costs included drug costs only (excluding administration fees). FN-related costs included all FN-related health care utilizations that were defined as having neutropenia, fever, or infection diagnosis. Per-patient per-cycle (PPPC) out-of-pocket (OOP) costs, health plan costs, and total costs were compared between originator (excluding on-body injector) and biosimilars users in the first cycle. A generalized linear model and a 2-part model were used. RESULTS: A total of 1,930 patients were included, of whom 884 (45.8%) used pegfilgrastim originator, 427 (22.1%) used pegfilgrastim-jmdb, and 619 (32.1%) used pegfilgrastim-cbqv. Adjusted PPPC OOP pegfilgrastim costs in the first cycle were significantly lower for the biosimilars vs the originator ($182 for pegfilgrastim-jmdb and $159 for pegfilgrastim-cbqv vs $299 for originator, P < 0.0001 for both comparisons). However, there was no difference in health plan costs ($5,783 for pegfilgrastim-jmdb and $5,845 for pegfilgrastim-cbqv vs $5,618 for originator) and total costs. In addition, no difference was observed for adjusted PPPC FN treatment and management OOP costs, health plan costs, and total costs in the first cycle. FN treatment OOP costs were $192 for originator, $197 for pegfilgrastim-jmdb (P = 0.958), and $240 for pegfilgrastim-cbqv (P = 0.680). FN treatment health plan costs were $2,804 for originator, $2,970 for pegfilgrastim-jmdb (P = 0.692), and $2,745 for pegfilgrastim-cbqv (P = 0.879). CONCLUSIONS: In a commercially insured population, using pegfilgrastim biosimilars in the first cycle for primary prophylaxis of FN led to cost savings for patients but not payers. No difference in FN-related costs was observed.