Risk of Nonmelanoma Skin Cancer in Association With Use of Hydrochlorothiazide-Containing Products in the United States.

Background: European studies reported an increased risk of nonmelanoma skin cancer associated with hydrochlorothiazide (HCTZ)-containing products. We examined the risks of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) associated with HCTZ compared with angiotensin-converting enzyme inhibitors (ACEIs) in a US population. Methods: We conducted a retrospective cohort study in the US Food and Drug Administration's Sentinel System. From the date of HCTZ or ACEI dispensing, patients were followed until a SCC or BCC diagnosis requiring excision or topical chemotherapy treatment on or within 30 days after the diagnosis date or a censoring event. Using Cox proportional hazards regression models, we estimated the hazard ratios (HRs), overall and separately by age, sex, and race. We also examined site- and age-adjusted incidence rate ratios (IRRs) by cumulative HCTZ dose within the matched cohort. Results: Among 5.2 million propensity-score matched HCTZ and ACEI users, the incidence rate (per 1000 person-years) of BCC was 2.78 and 2.82, respectively, and 1.66 and 1.60 for SCC. Overall, there was no difference in risk between HCTZ and ACEIs for BCC (HR = 0.99, 95% confidence interval [CI] = 0.97 to 1.00), but there was an increased risk for SCC (HR = 1.04, 95% CI = 1.02 to 1.06). HCTZ use was associated with higher risks of BCC (HR = 1.09, 95% CI = 1.07 to 1.11) and SCC (HR = 1.15, 95% CI = 1.12 to 1.17) among Caucasians. Cumulative HCTZ dose of 50 000 mg or more was associated with an increased risk of SCC in the overall population (IRR = 1.19, 95% CI = 1.05 to 1.35) and among Caucasians (IRR = 1.27, 95% CI = 1.10 to 1.47). Conclusions: Among Caucasians, we identified small increased risks of BCC and SCC with HCTZ compared with ACEI. Appropriate risk mitigation strategies should be taken while using HCTZ.

Risk of Psychiatric Adverse Events Among Montelukast Users.

BACKGROUND: There have been conflicting results from observational studies regarding the risk of psychiatric adverse events (PAEs) with montelukast use. OBJECTIVE: To determine whether there are associations of depressive disorders, self-harm, and suicide with use of montelukast compared with inhaled corticosteroid (ICS) use. METHODS: Using data from the Sentinel Distributed Database from January 1, 2000, to September 30, 2015, patients (n = 457,377) exposed to montelukast or ICS, aged 6 years and older with a diagnosis of asthma, were matched 1:1 on propensity scores. Hazard ratios (HRs) and 95% CIs were estimated for each study outcome overall and by age, sex, psychiatric history, and pre-/post-2008 labeling updates using Cox proportional hazards regression models. RESULTS: Exposure to montelukast was associated with a lower risk of treated outpatient depressive disorder (HR, 0.91; 95% CI, 0.89-0.93). No increased risks of inpatient depressive disorder (HR, 1.06; 95% CI, 0.90-1.24), self-harm (HR, 0.92; 95% CI, 0.69-1.21), or self-harm using a modified algorithm (HR, 0.81; 95% CI, 0.63-1.05) were observed with montelukast use compared with ICS use. Most PAEs occurred in the roughly one-third of patients having a past psychiatric history. CONCLUSIONS: When compared with use of ICS, we did not find associations between montelukast use and hospitalizations for depression or self-harm events. Our findings should be interpreted considering the study's limitations. Psychiatric comorbidity was common, and most PAEs occurred in patients with a past psychiatric history.

Understanding utilization patterns of biologics and biosimilars in the United States to support postmarketing studies of safety and effectiveness.

PURPOSE: To describe utilization of filgrastim and infliximab, the first two products with biosimilars approved in the United States. METHODS: We identified use of filgrastim (reference, tbo-filgrastim, and filgrastim-sndz) and infliximab (reference, infliximab-dyyb, and infliximab-abda) in the Sentinel Distributed Database using Healthcare Common Procedure Coding System (HCPCS) codes and National Drug Codes (NDCs) from January 2015 to August 2018. We calculated the proportion of use by code type and assessed uptake over time. We compared baseline patient characteristics and treatment indications. Among patients with >1 exposure episode, we characterized gaps between episodes. RESULTS: Use was identified primarily via HCPCS codes (filgrastim: 86.4%-97.7%; infliximab: 87.8%-100%) although some was identified via NDCs (filgrastim: 2.2%-13.5%; infliximab: <0.1%-6.5%). Filgrastim reference product use declined from 89.4% in January 2015 to 30.3% in June 2018, with corresponding increases in filgrastim-sndz (0% to 49.3%) and tbo-filgrastim (10.6% to 20.4%). Infliximab biosimilar uptake was low (9.7% in June 2018). We identified 94 846 filgrastim reference product, 27 143 tbo-filgrastim, and 38 264 filgrastim-sndz users. For infliximab, we identified 125 412 reference product, 1034 infliximab-dyyb, 49 infliximab-abda, and 4855 undetermined biosimilar users. Patients receiving filgrastim products were largely similar, but differences in age, sex, and indication were observed across infliximab product users. The median exposure episode gap ranged from 1 to 3 days for filgrastim and 48 to 50 days for infliximab. CONCLUSION: Use of biosimilar filgrastim has increased in the United States, but infliximab biosimilar use remains low. Data on identification of biosimilars in claims data and observed gaps between exposure episodes can be used to support drug safety studies of biosimilars.

Temporal Patterns in Chlamydia Repeat Testing in Massachusetts.

INTRODUCTION: National guidelines recommend test-of-cure for pregnant women and test-of-reinfection for all patients with chlamydia infections in order to interrupt transmission and prevent adverse sequelae for patients, partners, and newborns. Little is known about retesting and positivity rates, and whether they are changing over time, particularly in private sector practices. METHODS: Electronic health record data on patients with chlamydia tests were extracted from three independent clinical practice groups serving ≅20% of the Massachusetts population. Records were extracted using the Electronic medical record Support for Public Health platform (esphealth.org). These data were analyzed for temporal trends in annual repeat testing rates by using generalized estimating equations after index positive chlamydia tests between 2010 and 2015 and for differences in intervals to first repeat tests among pregnant females, non-pregnant females, and males. Data extraction and analysis were performed during calendar years 2017 and 2018. RESULTS: An index positive C. trachomatis result was identified for 972 pregnant female cases, 10,309 non-pregnant female cases, and 4,973 male cases. Test-of-cure 3-5 weeks after an index positive test occurred in 37% of pregnant females. Test-of-reinfection 8-16 weeks after an index positive test occurred in 39% of pregnant females, 18% of non-pregnant females, and 9% of males. There were no significant increases in test-of-cure or test-of-reinfection rates from 2010 to 2015. Among cases with repeat tests, 16% of pregnant females, 15% of non-pregnant females, and 16% of males had positive results. CONCLUSIONS: Chlamydia test-of-cure and test-of-reinfection rates are low, with no evidence of improvement over time. There are substantial opportunities to improve adherence to chlamydia repeat testing recommendations.

Opioid tolerance and urine drug testing among initiates of extended-release or long-acting opioids in Food and Drug Administration's Sentinel System.

OBJECTIVE: A risk evaluation and mitigation strategy for extended-release and long-acting (ER/LA) opioid analgesics was approved by the Food and Drug Administration in 2012. Our objective was to assess frequency of opioid tolerance and urine drug testing for individuals initiating ER/LA opioid analgesics. DESIGN: Retrospective cohort study. SETTING: Sentinel, a distributed database with electronic healthcare data on >190 million predominantly commercially insured members. PATIENTS, PARTICIPANTS: Members under age 65 initiating ER/LA opioid analgesics between January 2009 and December 2013. MAIN OUTCOME MEASURE(S): We examined the proportion of opioid-tolerant-only ER/LA opioid analgesic initiates meeting tolerance criteria: receipt of ≥30 mg oxycodone equivalents per day in 7 days prior to the first opioid-tolerant-only dispensing. We separately examined the proportion of new users of extended-release oxycodone (ERO) and other ER/LA opioid analgesics with a claim for a urine drug test in the 30 days prior to, and separately for the 183 days after, dispensing. RESULTS: We identified 79,824 ERO, 7,343 extended-release hydromorphone, and 91,778 transdermal fentanyl opi-oid-tolerant-only episodes. Tolerance criteria were met in 64 percent of ERO, 64 percent of extended-release hydromorphone and 40 percent of transdermal fentanyl episodes. We identified 210,581 incident ERO and 311,660 other ER/LA opioid analgesic episodes. Use of urine drug testing for ERO compared with other ER/LA opioid analgesics was: 4 percent vs 14 percent respectively in the 30 days prior to initiation and 9 percent vs 23 percent respectively in the 183 days following initiation. CONCLUSIONS: These results suggest potential areas for improving appropriate ER/LA opioid analgesic prescribing practices.